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Plasma soluneoplasmien (mukaan lukien multippeli myelooma) Hoito (PDQ®): Hoito - Terveys Professional Information [NCI]

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Plasma soluneoplasmien (mukaan lukien multippeli myelooma) Hoito

On olemassa useita erilaisia ​​plasman soluneoplasmien. Nämä sairaudet ovat kaikki liittyy monoklonaalisella (tai myelooma) proteiini (M-proteiini). Ne sisältävät monoklonaalinen merkityksen gammopatiassa (MGUS), eristetty plasmasytoomasolujen luun, ekstramedullaarinen plasmosytoomasolujen, ja useita myelooma.

Ilmaantuvuus ja kuolleisuus

Arvioitu uutta tapausta ja kuolemantapauksia multippelimyelooma Yhdysvalloissa vuonna 2012: [1]

Uudet asiat: 21,700.Deaths: 10710.

Kliininen esittely ja arviointi

Taulukko 1. Kliiniset esittäminen Plasma soluneoplasmien

Plasma Cell kasvain M proteiinityypin Patologia Kliiniset Esittely
MGUS = monoklonaalinen gammopatiassa merkitystä.
MGUS IgG-kappa- tai lambda-; tai IgA kappa tai lambda <10% plasman luuytimessä Oireeton, minimaalisella todisteita taudista (lukuun ottamatta läsnäolo M-proteiinia) [2]
Yksittäisiä plasmasytooma luun IgG-kappa- tai lambda-; tai IgA kappa tai gamma Solitary vaurion luun; <10% plasman soluja luuytimestä välinpitämättömästi sivuston Oireeton tai oireenmukaista
Extramedullary plasmasytooma IgG-kappa- tai lambda-; tai IgA kappa tai gamma Solitary vaurion pehmytkudoksen; yleisimmin esiintyy nenänielussa, risat, tai nenän sivuonteloiden [3] Oireeton tai oireenmukaista
Multippeli myelooma IgG-kappa- tai lambda-; tai IgA kappa tai gamma Usein useita leesioita luun Oireellinen

Arviointi potilailla, joilla on monoklonaalinen (tai myelooma) proteiini (M-proteiini)

Idiotyyppistä myeloomasolut löytyy verestä myeloomapotilaita kaikissa vaiheissa taudin. [4,5] Tästä syystä, kun hoito on aiheellista, systeeminen hoito on pidettävä kaikille potilaille, joilla on oireinen plasman soluneoplasmien. Potilaat, joilla on MGUS tai oireeton, kytevä myeloomaa eivät vaadi välitöntä hoitoa, mutta on noudatettava huolellisesti merkkejä taudin etenemisestä.

Suurena haasteena on erottaa vakaa, oireeton ryhmä potilaita, jotka eivät vaadi hoitoa potilaille, joilla on etenevä, oireenmukaista myeloomaa jotka tulee hoitaa heti. [6,7]

Potilaat, joilla on monoklonaalinen (tai myelooma) proteiini (M-proteiini) seerumissa ja / tai virtsan arvioidaan joidenkin seuraavat kriteerit:

Mittaa ja seuraa seerumin M-proteiinin seerumin elektroforeesilla tai erityiset immunoglobuliini määrityksiä; kuitenkin, erityiset immunoglobuliini määrällisesti aina yliarvioi M-proteiini, koska normaali immunoglobuliini sisältyvät tulokseen. Tästä syystä lähtötilanteessa ja seuranta mittaukset M-proteiinin pitäisi tehdä samalla menetelmällä. [8] määrälliset seerumitonta kevytketjuja voi olla hyödyllistä seurata toiminnan, jos M-proteiini ei ole apparent.Measure ja seuraa määrä M-proteiinin kevytketjut erittyy virtsaan 24 tunnin aikana. Mittaa proteiinin kokonaismäärän erittyy 24 tunnin aikana ja kertoo tämän arvon prosenttiosuus virtsan proteiini, joka on M-proteiini, joka määritetään elektroforeesilla väkevää virtsaa proteiinia. Helpompaa, mutta vähemmän tarkka, menetelmässä käytetään paikalla-virtsan proteiinin electrophoresis.Identify raskaan ja kevyen ketjun M-proteiinin, jonka immunofixation electrophoresis.Measure hemoglobiini, leukosyyttien, verihiutaleiden, ja ero counts.Sometimes, prosenttiosuuden määrittämiseksi luuytimen plasman soluja. Ole tietoinen siitä, että luuytimen plasmasolu jakelu voi vaihdella eri sites.Measure seerumivapaissa kappa ja lambda kevyt ketju. Tämä on erityisen hyödyllistä silloin, oligosecretory plasmasolu dyskrasia tai seuraavissa tapauksissa valon ketjun amyloidoosi. [9] Ota neula aspiraatteja yksinäinen lyyttisiä luuvaurion, ekstramedullaarinen kasvain (s), tai laajentunut imusolmuke (t) selvittää, onko näitä ovat plasmacytomas.Evaluate munuaisten toiminta, joiden seerumin kreatiniini ja kreatiniinin clearance.Electrophoresis väkevää virtsaa proteiini on erittäin hyödyllistä erottaa glomerulusten vauriot pyöröneulotusta vaurioita. Glomerulusten vauriot, kuten ne, jotka johtuvat glomerulusten talletukset amyloidi tai kevyen ketjun laskeuma tauti, johtaa epäselektiivisten vuoto kaikkien seerumiproteiinien virtsaan; elektroforeesikuviossa tämän virtsan muistuttaa seerumin kuvio voittopuolisesti albumiinia.

Useimmilla myeloomapotilaat, glomerulusten toimivat normaalisti sallii vain pienen molekyylipainon proteiinit, kuten kevyitä ketjuja, suodattaa virtsaan. Proteiinin pitoisuus dentiinitubuluksiin kasvaa, kun vettä imeytyy takaisin. Tämä johtaa sademäärä proteiinien ja muodostumista putkimainen heittoja, jotka voivat vahingoittaa tubulussoluihin. Kun putkimainen vaurioita, tyypillinen elektroforeesikuviossa näyttää pieni albumiinin huippu ja suurempi kevyen ketjun huippu globulin alueella; tämä putkimainen malli on tavanomaisia ​​malleja löytyy myeloomaa sairastavilla potilailla.

Mittaa seerumin kalsium-, AFOS, maitohappodehydrogenaasi, ja kun osoitetaan kliinisiä oireita, Kryoglobuliinit ja seerumin viscosity.Obtain röntgenkuvia kallo, kylkiluut, selkäranka, lantion, hartiaseudun, ja pitkät luut. Koko kehon, pieniannoksisen, nonenhanced multidetector tietokonetomografia ja magneettikuvaus (MRI) ovat selvityksen toimenpiteistä hoidon vasteen seurannassa. [10,11] magneettikuvauksessa selkärangan tai pitkät luut on herkempi havaitsemaan lyyttisiä vaurioita, mutta kaikki prognostinen tai terapeuttinen arvo tämän tiedon on vielä määrittämättä. [11] Suorita MRI jos paraspinal massa havaitaan tai jos oireet viittaavat selkäytimen tai hermojuuren compression.If amyloidoosi epäillään, suorittaa punktiomenetelmällä ihonalaisen vatsan rasvaa ja likaa luuydinbiopsianäytteissä amyloidin niin helpoin ja turvallisin tapa vahvistaa diagnoosin. [12] Mittaa seerumialbumiinin ja beeta-2-mikroglobuliini itsenäisinä ennustavia tekijöitä. [13,14] korkea plasmasolu merkintöjä indeksi (≥3%) tai esiintyminen verenkierrossa myeloomasolut pidetään huonona ennustavia tekijöitä. [15]

Nämä alustavat tutkimukset pitäisi verrata myöhemmin arvot myöhemmin, kun se on tarpeen päättää, onko tauti on stabiili tai etenevä, hoitovastetta, tai pahenee.

Kuten edellä mainittiin, suuri haaste on erottaa vakaa, oireeton ryhmä potilaita, jotka eivät vaadi hoitoa potilaille, joilla on etenevä, oireenmukaista myeloomaa jotka tulee hoitaa heti. [6,7]

Monoklonaalisia merkityksen gammopatiassa (MGUS)

Potilaat, joilla MGUS on M-proteiini seerumissa ilman havaintoja multippelimyelooma makroglobulinemia, amyloidoosi tai lymfooma ja on vähemmän kuin 10% plasman soluja luuytimessä. [2,16,17,18] Potilaat, joilla kytee myelooma on samanlaiset ominaisuudet, mutta se voi olla enemmän kuin 10% plasman soluja luuytimessä.

Tämäntyyppiset potilaat ovat oireettomia, ja ei pitäisi käsitellä. Niiden on kuitenkin noudatettava tarkasti, koska noin 1%: sta 2%: MGUS potilasta vuodessa etenee kehittää myelooma (yleisimmin), amyloidoosi, lymfooma, tai krooninen lymfaattinen leukemia ja voi sitten vaatia hoitoa. [18,19,20 ]

Lähes kaikissa tapauksissa multippelimyelooma edeltää asteittain nouseva taso MGUS. [21,22,23]

Riskitekijöitä, jotka ennustavat taudin etenemistä ovat seuraavat:

Epänormaali seerumittomassa kevyen ketjun ratio.Non-IgG-luokan MGUS.A korkea seerumin M-proteiinin taso (≥15 g / l). [24]

Yksittäisiä Plasmasy- Bone

Potilaalla on eristetty plasmasytoomasolujen luun, jos seuraavat löytyy:

Yksinäinen lyyttisiä vaurion plasman soluja löytyy luuston kysely muuten oireeton patient.A Luuydintutkimus päässä sivullisten sivusto sisältää alle 10% plasman soluja. [25,26,27]

Kun on kliinisesti osoitettu, MRI voi paljastaa aavistamaton luinen vaurioita, jotka havaitsematta vakio röntgenkuvat. MRI koko selkärangan voi tunnistaa muita luinen vaurioita. [28]

Extramedullary Plasmasy-

Potilaalla on ekstramedullaarinen plasmasytoomasolujen jos seuraavat löytyy:

Eristetty plasma-solu kasvaimia pehmytkudosten, yleisimmin esiintyvät risat, nenänielun tai sivuonteloiden sinuses.Negative havainnot luuston röntgenkuvat ja luuydinbiopsianäytteissä. [29,30,31]

Useita myelooma

Multippeli myelooma on systeeminen pahanlaatuisuus plasman soluja, jotka tyypillisesti liittyy useita sivustoja luuytimessä ja erittää kokonaan tai osittain monoklonaalinen vasta-aine.

Ennuste

Useita myelooma on hyvin hoidettavissa, mutta harvoin parannettavissa. Mediaani selviytyminen prechemotherapy aikakausi oli noin 7 kuukautta. Käyttöönoton jälkeen kemoterapiaa, ennuste parani merkittävästi mediaanielossaolosta 24-30 kuukautta ja 10 vuoden pysyvyys on 3%. Entisestään parannuksia ennuste on tapahtunut, koska käyttöönotto uudempia hoitoja kuten pulssin kortikosteroidit, talidomidi, bortetsomibin, ja autologisen ja allogeenisen kantasolusiirron mediaani jäänteitä 45-60 kuukautta. [32,33,34]

Useita myelooma on potentiaalisesti parannettavissa, kun se esittelee yksinäinen plasmasytoomasolujen luun tai ekstramedullaarinen plasmasytooma. (Katso Yksittäisiä Plasmasy- Bone ja ekstramedullaarisissa Plasmasy- kohdat tämän tiivistelmän lisätietoja.)

Amyloidoosi liittyvä Plasma soluneoplasmien

Useita myelooma ja muut plasman soluneoplasmien voi aiheuttaa sairaus nimeltä amyloidoosi. Ensisijainen amyloidoosi voi aiheuttaa vakavia elintoimintahäiriöstä etenkin munuaisissa, sydämessä tai ääreishermojen. Kohonneita seerumin sydämen troponiinit ja aivojen natriureettinen peptidi ovat köyhiä ennustavat tekijät. Ehdotettu lavastus järjestelmä ensisijainen systeeminen amyloidoosi perustuu näihin seerumin vaatii riippumatonta ja mahdollisille vahvistusta. [35]

Viitteet:

1. American Cancer Society .: Syöpä Faktat ja luvut 2012. Atlanta, Ga: American Cancer Society, 2012. Saatavilla verkossa. Viimeksi näytetty 14 kesäkuu 2012.
2. Kyle RA, Rajkumar SV: monoklonaalisia merkityksen gammopatiassa ja kytevä multippelimyelooma: korostaminen riskitekijöitä etenemisen. Br J Haematol 139 (5): 730-43, 2007.
3. Knowling MA, Harwood AR, Bergsagel DE: vertailu ekstramedullaarinen plasmasytoomiin kanssa yksinäinen ja useita plasman kasvaimet luun. J. Clin Oncol 1 (4): 255-62, 1983.
4. Zandecki M, Facon T, Preudhomme C, et al .: merkitys kiertävästä plasman solujen multippeli myelooma. Leuk lymfooma 14 (5-6): 491-6, 1994.
5. Billadeau D, Van Ness B, Kimlinger T, ym .: Klonaaliset verenkierrossa solut ovat yleisiä plasmassa soluproliferatiivisia häiriöt: vertailu monoklonaalinen merkityksen gammopatiassa, kytevän multippelimyeloomaa ja aktiivinen myelooma. Veren 88 (1): 289-96, 1996.
6. Hän Y, Wheatley K, Clark O, et al .: Early versus laskennallinen hoito alkuvaiheessa useita myelooma. Cochrane Database Syst Rev (1): CD004023, 2003.
7. Kyle RA, Remstein ED, Therneau TM, ym .: Clinical kulkuun ja ennusteeseen kytevä (oireeton) multippeli myelooma. N Engl J Med 356 (25): 2582-90, 2007.
8. Riches PG, Sheldon J, Smith AM, et al .: yliarviointi monoklonaalinen immunoglobuliinille immunokemiallisia menetelmillä. Ann Clin Biochem 28 (Pt 3): 253-9, 1991.
9. Dispenzieri, Kyle R, Merlini G, ym .: Kansainvälinen Myelooma työryhmän suuntaviivat seerumitonta kevytketju analyysi multippelimyelooma ja niihin liittyviä häiriöitä. Leukemia 23 (2): 215-24, 2009.
10. Hörger M, Kanz L, Denecke B, ym .: hyöty käyttämällä koko kehon pieniannoksinen, nonenhanced, multidetector tietokonetomografia seurantaa ja hoidon vasteen seurannassa potilailla, joilla on useita myelooma. Syöpä 109 (8): 1617-26, 2007.
11. Walker R, Barlogie B, Haessler J, ym .: Magneettikuvaus useita myelooma: diagnostiset ja kliiniset vaikutukset. J Clin Oncol 25 (9): 1121-8, 2007.
12. Gertz MA, Li CY, Shirahama T, ym .: Utility ihonalaisen rasvan toive diagnoosi systeeminen amyloidoosi (immunoglobuliini kevytketju). Arch Intern Med 148 (4): 929-33, 1988.
13. Greipp PR: Ennakot diagnosointiin ja hoitoon myelooma. Semin Hemato 29 (3 Suppl 2): ​​24-45, 1992.
14. Durie BG Kanta-Novack D, Salmon SE, et al .: Prognostic arvo esikäsittelyyn seerumin beeta 2 mikroglobuliinin myelooma: Varsinais Syöpätautien Group Study. Veri 75 (4): 823-30, 1990.
15. Greipp PR, Witzig T: Biologia ja myelooman hoitoa. Curr Opin Oncol 8 (1): 20-7, 1996.
16. Kyle RA, Therneau TM, Rajkumar SV, et al .: yleisyys monoklonaalinen gammopatiassa merkitystä. N Engl J Med 354 (13): 1362-9, 2006.
17. Kansainvälinen Myeloma työryhmä .: Perusteet luokittelusta monoklonaalinen gammopathies, multippeli myelooma ja siihen liittyvät sairaudet: raportti International Myeloma työryhmän. Br J Haematol 121 (5): 749-57, 2003.
18. Bird J, Behrens J, Westin J, ym .: UK Myelooma Forum (UKMF) ja Nordic Myelooma Study Group (NMSG): suuntaviivat tutkinnassa havaittuja M-proteiinit ja hallinta monoklonaalinen merkityksen gammopatiassa (MGUS) . Br J Haematol 147 (1): 22-42, 2009.
19. Attal M, Harousseau JL, Stoppa AM, ym .: prospektiivisessa satunnaistetussa tutkimuksessa autologisen luuytimensiirron ja kemoterapiaa multippeli myelooma. Intergroupe Français du Myelome. N Engl J Med 335 (2): 91-7, 1996.
20. Kyle RA, Therneau TM, Rajkumar SV, et al .: pitkäaikainen tutkimus ennusteeseen monoklonaalinen gammopatiassa merkitystä. N Engl J Med 346 (8): 564-9, 2002.
21. Weiss BM, Abadie J, Verma P, et al .: monoklonaalinen gammopatia edeltää multippelimyelooma useimmilla potilailla. Veri 113 (22): 5418-22, 2009.
22. Landgren O, Kyle RA, Pfeiffer RM, et al .: monoklonaalisia merkityksen gammopatiassa (MGUS) johdonmukaisesti edeltää multippelimyelooma: ennakoiva tutkimus. Veri 113 (22): 5412-7, 2009.
23. Blade J, Rosiñol L, Cibeira MT: Ovatko kaikki myeloomat edeltää MGUS? Veri 113 (22): 5370, 2009.
24. Rajkumar SV, Kyle RA, Therneau TM, ym .: Seerumittomuuteen kevytketju suhde on itsenäinen riskitekijä etenemisen monoklonaalinen gammopatiassa merkitystä. Veren 106 (3): 812-7, 2005.
25. Ozsahin M, Tsang RW, Poortmans P, et al .: Outcomes ja kuvioita epäonnistumisen yksinäinen plasmasytoomasolujen: monikeskustutkimus Harvinainen syöpäverkoston tutkimuksessa 258 potilasta. Int J Radiat Oncol Biol Phys 64 (1): 210-7, 2006.
26. Dimopoulos MA, Moulopoulos LA, Maniatis, et al .: Solitary plasmasytoomasolujen luun ja oireeton useita myelooma. Veren 96 (6): 2037-44, 2000.
27. Dimopoulos MA, Hamilos G: Solitary luu plasmasytoomasolujen ja ekstramedullaarinen plasmasytooma. Curr Kohtele Valinnat Oncol 3 (3): 255-9, 2002.
28. Liebross RH, Ha CS, Cox JD, et al .: Solitary luu plasmasytoomasolujen: tulos ja ennustavia tekijöitä sädehoidon. Int J Radiat Oncol Biol Phys 41 (5): 1063-7, 1998.
29. Tournier-Rangeard L, Lapeyre M, Graff-Caillaud P, et al .: Sädehoito yksinäinen ekstramedullaarinen plasmasytoomasolujen pään ja kaulan alueen: annos on yli 45 Gy kohdetilavuudesta parantaa paikallista valvontaa. Int J Radiat Oncol Biol Phys 64 (4): 1013-7, 2006.
30. Michalaki VJ, Hall J, Henk JM, et al .: Lopulliset sädehoito ekstramedullaarinen plasmasytoomiin pään ja kaulan. Br J Radioi 76 (910): 738-41, 2003.
31. Alexiou C, Kau RJ, Dietzfelbinger H, ym .: ekstramedullaarinen plasmasytoomasolujen: kasvain esiintyminen ja terapeuttinen käsitteitä. Cancer 85 (11): 2305-14, 1999.
32. Kumar SK, Rajkumar SV, Dispenzieri, et al .: Parempi hengissä useita myelooma ja vaikutukset Uusien hoitomuotojen. Veri 111 (5): 2516-20, 2008.
33. Ludwig H, Durie BG, Bolejack V, ym .: myelooma potilailla alle 50 vuoden ikä esittelee edullisempia ominaisuuksia ja näyttää parempi selviytyminen: analyysi 10 549 potilasta International Myeloma työryhmän. Veri 111 (8): 4039-47, 2008.
34. Brenner H, Gondos, Pulte D: Viimeisin merkittävä parannus pitkän aikavälin eloonjäämistä nuoremmilla potilailla, joilla on useita myelooma. Veri 111 (5): 2521-6, 2008.
35. Dispenzieri, Gertz MA, Kyle RA, et al .: Seerumin sydämen troponiinit ja N-terminaalinen pro-brain natriureettinen peptidi: lavastus järjestelmä ensisijainen systeeminen amyloidoosi. J Clin Oncol 22 (18): 3751-7, 2004.

Ei yleisesti hyväksytty lavastus järjestelmä olemassa monoklonaalinen merkityksen gammopatiassa (MGUS), eristetty plasmosytoomasolujen luun tai ekstramedullaarinen plasmasytooma. Plasman soluneoplasmien, lavastus järjestelmä on olemassa ainoastaan ​​useita myelooma.

Useita myelooma

Useita myelooma on lavastettu arvioimalla myelooma tuumorisolun massa perusteella määrän monoklonaalisia (tai myelooma) proteiini (M-proteiini) seerumissa ja / tai virtsa, sekä erilaisia ​​kliinisiä parametrejä, kuten hemoglobiinin ja seerumin kalsiumpitoisuus, määrä lyyttinen luuleesioita, ja läsnäolo tai puuttuminen munuaisten vajaatoiminta. Munuaisten vajaatoiminta pahenee ennustetta riippumatta vaiheessa.

Vaiheessa taudin esitys on vahva tekijä selviytymisen, mutta sillä on vain vähäinen vaikutus valintaan hoidon, koska lähes kaikki potilaat, lukuun ottamatta harvinaisia ​​potilailla, joilla on yksinäinen luukasvaimet tai ekstramedullaarinen plasmasytoomiin ovat yleistynyt tauti.

Kansainvälinen lavastus järjestelmä

Kansainvälinen Myeloma työryhmä tutkittu 11171 potilasta, joista 2901 sai korkean annoksia ja 8270 sai vain standardi-lääkityksen. [1]

Kansainvälinen vaiheittainen järjestelmä on peräisin, ja on esitetty alla olevassa taulukossa 2. [1]

Taulukko 2. Kansainvälinen Staging System Useita myelooma

Vaihe Perusteet Mediaani Survival (MO)
Minä Beeta-2-mikroglobuliini <3,5 mg / l ja albumiini ≥3.5 g / l 62
II Beta-2-mikroglobuliini <3,5 mg / l ja albumiini <3,5 g / dl tai beeta-2-mikroglobuliini 3,5 mg / L <5,5 mg / l 44
III Beeta-2-mikroglobuliini ≥5.5 mg / l 29

Geneettiset tekijät ja riskiryhmien

Geneettinen kromosomipoikkeavuuksien havaita interfaasivaiheessa fluoresenssi in situ hybridisaatio (FISH) voi määritellä prognostista ryhmien retrospektiivi ja ennakoivia arvioita. [2,3] Lyhyt selviytymisen ja lyhyemmän aikaa hoitovaste on raportoitu t (4; 14) (p16; q32 ), t (14; 16) (q32; q23), sytogeneettinen poistaminen 13q-14, ja poistaminen 17p13 (p53 lokus). [2,3,4,5,6] Kysymys siitä, onko valinta hoito perustuu kaloihin analyysi voi vaikuttaa lopputulokseen on odotettava lisätutkimus mahdollisille tutkimuksissa.

Uudemmat kliiniset tutkimukset kerrostamiselimen potilaalla on useita myelooma osaksi ns vakio-riskiryhmä, jonka osuus 75%: lla potilaista ja on mediaanielossaolosta 3-6 vuotta, ja riskiryhmään, joka on mediaanielossaolosta alle 3 vuotta. [2,3,4,5,6,7] (Katso taulukko 3 alla.) Tämä jaottelu, joka perustuu sytogeneettiseen havaintojen on johdettu retrospektiivinen analyysi ja vaatii mahdollisille validointi. [7] Luuydinnäytteet jotka toimitetaan sytogeneettinen ja FISH analyysi. Plasma soluleukemia on erityisen huono ennuste. [8]

Taulukko 3. riskiryhmät Useita myelooma

Risk Group Sytogeneettiset Havainnot Tauti Ominaisuudet
KALAT = fluoresenssi in situ.
Standard riski Onko jokin seuraavista sytogeneettinen havainnot: (1) ei ole haitallisia kalaa tai sytogenetiikka, (2) hyperdiploidy, (3) t (11; 14) FISH, tai (4) t (6; 14) FISH. Nämä potilaat useimmiten (1) sairaus, joka ilmaisee IgG kappa monoklonaalinen gammopathies ja (2) lyyttisiä luuleesioiden.
Korkea riski Onko jokin seuraavista sytogeneettinen havainnot: (1) del 17p FISH, (2) t (4; 14) FISH, (3) t (14; 16) FISH, (4) sytogeneettinen del 13, tai (5 ) hypodiploidy. Näillä potilailla on (1) sairaus, joka ilmaisee IgA lambda monoklonaalisia gammopathies (usein) ja (2) luustoon liittyvät komplikaatiot (harvemmin).

Viitteet:

1. Greipp PR, San Miguel J, Durie BG, et al .: Kansainvälinen lavastus järjestelmä multippeli myelooma. J Clin Oncol 23 (15): 3412-20, 2005.
2. Fonseca R, Blood E, Rue M, et al .: Clinical ja biologinen seuraukset toistuvat genomista poikkeavuuksia myelooma. Veri 101 (11): 4569-75, 2003.
3. Avet-Loiseau H, Attal M, Moreau P, et al .: Geneettinen poikkeavuuksia ja eloonjäämisen multippelimyelooma: kokemus Intergroupe ranskankielisten du Myelome. Veri 109 (8): 3489-95, 2007.
4. Gertz MA, Lacy MQ, Dispenzieri, et al .: Clinical vaikutukset t (11; 14) (q13; q32), t (4; 14) (p16.3; q32), ja -17p13 myeloomapotilailla hoidettiin korkea-lääkityksen. Veri 106 (8): 2837-40, 2005.
5. Gutiérrez NC, Castellanos MV, Martín ML, et al .: Prognostic ja biologiset vaikutukset geneettisten poikkeavuuksien multippelimyelooma meneillään autologisen kantasolusiirron: t (4; 14) on eniten merkitystä haitalliset ennustetekijä, kun taas RB poistetaan ainutlaatuisena poikkeavuus ei liity haitallisia ennustetta. Leukemia 21 (1): 143-50, 2007.
6. Sagaster V, Ludwig H, Kaufmann H, ym .: Bortetsomibilla relapsoituneessa multippeli myelooma: hoitovasteen ja vasteen kesto ovat riippumattomia kromosomin 13q-poisto. Leukemia 21 (1): 164-8, 2007.
7. Kumar SK, Mikhael JR, Buadi FK, et al .: hallinta äskettäin diagnosoitu oireenmukaista useita myelooma: päivitetty Mayo ositus myelooma ja Risk-Mukautettu Therapy (mSMART) hoitosuosituksia. Mayo Clin Proc 84 (12): 1095-110, 2009.
8. Ramsingh G, Mehan P, Luo J, ym .: Ensisijainen plasma soluleukemia: seurannan, epidemiologian ja Lopputulokset tietokanta analyysi vuosien 1973 ja 2004. Syöpä 115 (24): 5734-9, 2009.

Suuri haaste hoidettaessa plasmassa soluneoplasmien on erottaa vakaa, oireeton ryhmä potilaita, jotka eivät vaadi välitöntä hoitoa potilaille, joilla on etenevä, oireenmukaista myeloomaa jotka tulee hoitaa heti. [1,2] monoklonaalisia merkityksen gammopatiassa tai kytevän myelooma on erotettava progressiivinen myelooma.

Oireeton Plasma soluneoplasmien

Oireettomilla potilailla, joilla on useita myeloomaa, joilla ei ole lyyttisiä luuleesioita ja normaali munuaisten toiminta voidaan aluksi havaita turvallisesti ulkopuolella yhteydessä kliinisessä tutkimuksessa. [1,3,4] lisääminen anemia on luotettavin mittari etenemisen. [4]

Oireista Plasma soluneoplasmien

Hoito tulisi antaa potilaille, joilla on oireinen tauti on edennyt pitkälle.

Hoito tulee suunnata vähentämään kasvainsolujen taakkaa ja käännetään mitään komplikaatioita sairauden, kuten munuaisten vajaatoiminta, infektio, hyperviskositeettiin tai hyperkalsemia, jossa asianmukainen lääketieteellinen hoito. (Katso PDQ yhteenveto Hyperkalsemiaa lisätietoja.)

Vasteen kriteerit on kehitetty potilaiden kliinisiin tutkimuksiin. [5]

Nykyinen hoito potilailla, joilla on oireinen myeloomaa voidaan jakaa seuraaviin ryhmiin:

Induktio therapies.Consolidation hoitoja, jotka ovat vähemmän sovelletaan erittäin elderly.Maintenance therapies.Supportive hoito, kuten bisfosfonaattien. (Katso adjuvantti huumeita osio Pharmacologic Management osassa PDQ yhteenveto Pain lisätietoja.)

Viitteet:

1. Hän Y, Wheatley K, Clark O, et al .: Early versus laskennallinen hoito alkuvaiheessa useita myelooma. Cochrane Database Syst Rev (1): CD004023, 2003.
2. Kyle RA, Remstein ED, Therneau TM, ym .: Clinical kulkuun ja ennusteeseen kytevä (oireeton) multippeli myelooma. N Engl J Med 356 (25): 2582-90, 2007.
3. Riccardi, Mora O, Tinelli C, et al .: pitkäaikainen säilyminen vaiheen I multippelimyelooma antanut kemoterapiaa juuri diagnoosin jälkeen tai sairauden etenemisen: monikeskustutkimus satunnaistetussa tutkimuksessa. Osuuskunta ryhmä Tutkimus ja hoito Useita myelooma. Br J Cancer 82 (7): 1254-60, 2000.
4. Blade J, Dimopoulos M, Rosiñol L, et al .: Smoldering (oireeton) multippeli myelooma: nykyinen diagnostiset kriteerit, uusia ennustajia tuloksista, ja seuranta suosituksia. J Clin Oncol 28 (4): 690-7, 2010.
5. Durie BG, Harousseau JL, Miguel JS, et al .: Kansainvälinen yhdenmukaista ratkaisua kriteerit multippeli myelooma. Leukemia 20 (9): 1467-73, 2006.

Standard Hoitovaihtoehtoja Amyloidoosi liittyvä Plasma soluneoplasmien

Standard hoitovaihtoehtoja amyloidoosi liittyy plasman soluneoplasmien ovat seuraavat:

1. Kemoterapiaa.
2. Kantasolujen pelastus.

Kemoterapia

Kaksi satunnaistettua tutkimusta osoitti pitkäaikainen yleinen (OS) kanssa suun kautta kemoterapia melfalaanin kanssa tai ilman kolkisiini vs. kolkisiinia yksin. [1,2] [Todisteiden taso: 1iiA]

Kuten pätee kaikkiin plasmasolu dyscrasias, luulojen vastauksia amyloidoosi on raportoitu, kuten Lounais Syöpätautien konsernin oikeudenkäynti (SWOG-9628 [NCT00002849]), deksametasonille yksin ja yhdistelminä, sekä talidomidi, syklofosfamidi, melfalaani, bortetsomibin, ja lenalidomidia. [3,4,5,6,7,8]

Kantasolujen pelastus

Satunnaistettu, prospektiivinen tutkimus 100 potilaalla on immunoglobuliini amyloidoosi kevytketju verrattuna melfalaania plus deksametasonia suurina annoksina korkean annoksen melfalaania plus autologisen kantasolujen pelastus. [9]

Kun seuranta-ajan mediaani oli 3 vuotta, mediaani suosi nontransplant varsi (56,9 kuukautta vs. 22,2 kuukautta; p = 0,04). [9] [Todisteiden taso: 1iiA] 24% elinsiirtoa liittyvää kuolleisuutta tässä sarjassa ja toiset heijastaa vaikeuksia korkea solunsalpaajahoito vanhemmilla potilailla, joilla elintoimintahäiriöstä. [9,10,11,12] satunnaistetussa tutkimuksessa vahvistetaan hyöty autologisesti ei odoteta. [13]

Empiirisiä sarja kuvaa koko intensiteetti ja vähentää intensiteetin allogeenisen kantasolusiirron. [14]

Nykyinen kliinisiä tutkimuksia

Tarkista USA kliinisiä tutkimuksia NCI: n luettelosta syövän kliinisissä tutkimuksissa, jotka ovat nyt hyväksyä potilailla, joilla on ensisijainen systeeminen amyloidoosi. Luettelo kliinisissä tutkimuksissa voidaan edelleen kaventaa sijainnin, huumeiden, interventio, ja muut kriteerit.

Yleistä tietoa kliinisistä tutkimuksista on saatavissa myös NCI verkkosivustosta.

Viitteet:

1. Kyle RA, Gertz MA, Greipp PR, ym .: oikeudenkäynti kolmen hoito perusasteen amyloidoosi: kolkisiinia yksin, melfalaanin ja prednisonin ja melfalaanin, prednisonin ja kolkisiinia. N Engl J Med 336 (17): 1202-7, 1997.
2. Skinner M, Anderson J, Simms R, ym .: hoito 100 primaarista amyloidoosi: satunnaistetussa tutkimuksessa melfalaania, prednisonin ja kolkisiini vs. kolkisiinia vain. Am J Med 100 (3): 290-8, 1996.
3. Dhodapkar MV, Hussein MA, Rasmussen E, ym .: Kliininen teho korkea-annos deksametasonia huolto deksametasoni / alfainterferoni- primaarista systeeminen amyloidoosi: tulokset Yhdysvallat työryhmän Trial Varsinais Syöpätautien Group (SWOG) S9628. Veri 104 (12): 3520-6, 2004.
4. Wechalekar AD, Goodman HJ, Lachmann HJ et al .: tehoa ja turvallisuutta riskien mukautettu syklofosfamidi, talidomidi ja deksametasoni systeemistä AL amyloidoosi. Veri 109 (2): 457-64, 2007.
5. Dispenzieri, Lacy MQ, Zeldenrust SR, et al .: aktiivisuus lenalidomidin tai ilman deksametasonia primaarista systeeminen amyloidoosi. Veri 109 (2): 465-70, 2007.
6. Sanchorawala V, Wright pääosasto, Rosenzweig M, et al .: Lenalidomidia ja deksametasonia hoidossa AL-amyloidoosi: tulokset vaiheen 2 tutkimuksessa. Veri 109 (2): 492-6, 2007.
7. Kastritis E, Wechalekar AD, Dimopoulos MA, et al .: Bortetsomibilla tai ilman deksametasonia ensisijainen systeeminen (kevytketju) amyloidoosi. J Clin Oncol 28 (6): 1031-7, 2010.
8. Moreau P, Jaccard, Benboubker L, et al .: Lenalidomidia yhdessä melfalaanin ja deksametasonin potilailla, joilla on äskettäin diagnosoitu AL-amyloidoosi: monikeskustutkimus vaihe 1/2 annoksensuurentamistutkimuksessa. Veri 116 (23): 4777-82, 2010.
9. Jaccard, Moreau P, Leblond V, ym .: Korkean annoksen melfalaania vs. melfalaania + deksametasoni AL-amyloidoosi. N Engl J Med 357 (11): 1083-93, 2007.
10. Dispenzieri, Kyle RA, Lacy MQ, et al .: Superior selviytymistä ensisijainen systeeminen amyloidoosi saavien potilaiden ääreisverenkierron kantasolujen siirron: tapauskontrollitutkimuksessa. Veri 103 (10): 3960-3, 2004.
11. Skinner M, Sanchorawala V Seldin DC, et al .: Korkean annoksen melfalaania ja autologisen kantasolusiirtoa potilailla, joilla on AL-amyloidoosi: 8 vuoden tutkimuksessa. Ann Intern Med 140 (2): 85-93, 2004.
12. Leung N, Leung TR, Cha SS, et al .: Liiallinen nesteen kertymistä kantasolujen mobilisaatio: romaani ennustetekijä ensimmäisen vuoden pysyvyys kantasolusiirron jälkeen AL-amyloidoosi potilailla. Veri 106 (10): 3353-7, 2005.
13. Mehta J, Gerta MA, Dispenzieri: Korkea-annos hoito amyloidoosi: alun loppu? Veri 103 (10): 3612-3, 2004.
14. Schönland SO, Lokhorst H, Buzyn, et al .: Allogeeniset ja syngeenisiä hematopoieettinen solutransplantaati- potilaalla on amyloidin kevytketjuiseen amyloidoosi: kertomus Euroopan Group for Blood ja luuydintransplantaatiota. Veri 107 (6): 2578-84, 2006.

Standard Hoitovaihtoehtoja monoklonaalisia merkityksen gammopatiassa (MGUS)

Standard hoitovaihtoehtoja MGUS kuuluvat seuraavat:

1. Valpas odottaa.

Valpas odottaa

Useita myelooma, muut plasmasolu dyskrasia tai lymfooma kehittyy 12%: lla potilaista 10 vuotta, 25% 20 vuotta, ja 30% 25 vuotta.

Kaikki potilaat, joilla MGUS olisi tarkkailtava havaita nousua M-proteiinin tasot ja kehittäminen plasmasolu dyskrasia. Korkeammalla alkuperäisen M-proteiinin tasot voivat korreloida lisääntynyt riski eteneminen multippeli myelooma. [1,2] Vuonna suuri retrospektiivinen raportti, etenemisen riskiä on 20 vuotta oli 14% alkuperäisestä monoklonaalinen proteiini tasolla 0,5 g / dl tai vähemmän, 25% tasolle 1,5 g / dl, 41% tasolle 2,0 g / dl, 49% ja taso 2,5 g / dl, ja 64% varten tasolle 3,0 g / dl. [1 ]

Hoito tapahtuu vasta taudin edetessä lavalle että oireet tai oireet tulevat.

Potilaat, joilla on MGUS tai kytevän myeloomaa eivät reagoi useammin, jotta pidemmän remissiot, tai ovat parantuneet selviytymisen jos kemoterapia aloitetaan aikaisin, kun ne ovat vielä oireettomia eikä odottaa etenemisen ennen hoidon aloittamista. [3,4,5,6] Uudempi hoitoja ei ole osoitettu ehkäistä tai viivästyttää etenemistä MGUS jotta plasmasolu dyskrasia. [2]

Nykyinen kliinisiä tutkimuksia

Tarkista USA kliinisiä tutkimuksia NCI: n luettelosta syövän kliinisissä tutkimuksissa, jotka ovat nyt hyväksyä potilailla, joilla on monoklonaalinen gammopatiassa merkitystä. Luettelo kliinisissä tutkimuksissa voidaan edelleen kaventaa sijainnin, huumeiden, interventio, ja muut kriteerit.

Yleistä tietoa kliinisistä tutkimuksista on saatavissa myös NCI verkkosivustosta.

Viitteet:

1. Kyle RA, Therneau TM, Rajkumar SV, et al .: pitkäaikainen tutkimus ennusteeseen monoklonaalinen gammopatiassa merkitystä. N Engl J Med 346 (8): 564-9, 2002.
2. Bird J, Behrens J, Westin J, ym .: UK Myelooma Forum (UKMF) ja Nordic Myelooma Study Group (NMSG): suuntaviivat tutkinnassa havaittuja M-proteiinit ja hallinta monoklonaalinen merkityksen gammopatiassa (MGUS) . Br J Haematol 147 (1): 22-42, 2009.
3. Blade J, Dimopoulos M, Rosiñol L, et al .: Smoldering (oireeton) multippeli myelooma: nykyinen diagnostiset kriteerit, uusia ennustajia tuloksista, ja seuranta suosituksia. J Clin Oncol 28 (4): 690-7, 2010.
4. Hän Y, Wheatley K, Clark O, et al .: Early versus laskennallinen hoito alkuvaiheessa useita myelooma. Cochrane Database Syst Rev (1): CD004023, 2003.
5. Riccardi, Mora O, Tinelli C, et al .: pitkäaikainen säilyminen vaiheen I multippelimyelooma antanut kemoterapiaa juuri diagnoosin jälkeen tai sairauden etenemisen: monikeskustutkimus satunnaistetussa tutkimuksessa. Osuuskunta ryhmä Tutkimus ja hoito Useita myelooma. Br J Cancer 82 (7): 1254-60, 2000.
6. Kyle RA, Remstein ED, Therneau TM, ym .: Clinical kulkuun ja ennusteeseen kytevä (oireeton) multippeli myelooma. N Engl J Med 356 (25): 2582-90, 2007.

Katso Waldenström makroglobulinemia osio PDQ yhteenveto Aikuiskoulutuksen Non-Hodgkinin lymfooma Hoito lisätietoja.

Standard Hoitovaihtoehtoja Yksittäisiä Plasmasy- Bone

Standard hoitovaihtoehtoja eristyksissä plasmasytoomasolujen luun kuuluvat seuraavat:

1. Sädehoitoa vaurion.
2. Chemotherapy (if the monoclonal [or myeloma] protein [M protein] increases and other evidence of symptomatic multiple myeloma occurs).

Radiation therapy

About 25% of patients have a serum and/or urine M protein; this should disappear following adequate radiation therapy to the lytic lesion.

The survival rate of patients with isolated plasmacytoma of bone treated with radiation therapy to the lesion is greater than 50% at 10 years, which is much better than the survival rate of patients with disseminated multiple myeloma.[1]

Kemoterapia

Most patients will eventually develop disseminated disease and require chemotherapy; almost 50% of them will do so within 2 years of diagnosis.[2,3] However, patients with serum paraprotein or Bence Jones protein, who have complete disappearance of these proteins after radiation therapy, may be expected to remain free of disease for prolonged periods.[2,4] Patients who progress to multiple myeloma tend to have good responses to chemotherapy with a median survival of 63 months after progression.[2,4]

Nykyinen kliinisiä tutkimuksia

Check for US clinical trials from NCI's list of cancer clinical trials that are now accepting patients with isolated plasmacytoma of bone. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

Yleistä tietoa kliinisistä tutkimuksista on saatavissa myös NCI verkkosivustosta.

Viitteet:

1. Tsang RW, Gospodarowicz MK, Pintilie M, et al.: Solitary plasmacytoma treated with radiotherapy: impact of tumor size on outcome. Int J Radiat Oncol Biol Phys 50 (1): 113-20, 2001.
2. Liebross RH, Ha CS, Cox JD, et al.: Solitary bone plasmacytoma: outcome and prognostic factors following radiotherapy. Int J Radiat Oncol Biol Phys 41 (5): 1063-7, 1998.
3. Dimopoulos MA, Moulopoulos LA, Maniatis A, et al.: Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood 96 (6): 2037-44, 2000.
4. Dimopoulos MA, Goldstein J, Fuller L, et al.: Curability of solitary bone plasmacytoma. J Clin Oncol 10 (4): 587-90, 1992.

Standard Treatment Options for Extramedullary Plasmacytoma

Standard treatment options for extramedullary plasmacytoma include the following:

1. Radiation therapy to the isolated lesion with fields that cover the regional lymph nodes, if possible.[1,2]
2. In some cases, surgical resection may be considered, but it is usually followed by radiation therapy.[2]
3. If the monoclonal (or myeloma) protein (M protein) persists or reappears, the patient may need further radiation therapy. In some patients, the plasmacytoma may shrink, but not disappear, and the M protein persists. These types of patients should be followed closely. Surgery should be performed if the plasmacytoma is in a site where it can be removed easily (eg, in the tonsil); the M protein may disappear from the blood or urine. In other cases, persistence or an increasing M protein may herald progression to multiple myeloma.
4. Chemotherapy is required if the disease progresses and causes symptoms.

Patients with isolated plasma cell tumors of soft tissues, most commonly occurring in the tonsils, nasopharynx, or paranasal sinuses, should have skeletal x-rays and bone marrow biopsy (both of which should be negative) and evaluation for M protein in serum and urine.[1,2,3,4]

About 25% of patients have serum and/or urine M protein; this should disappear following adequate radiation.

Extramedullary plasmacytoma is a highly curable disease with progression-free survival ranging from 70% to 87% at 10 to 14 years after treatment with radiation therapy (with or without previous resection).[1,2,5]

Nykyinen kliinisiä tutkimuksia

Check for US clinical trials from NCI's list of cancer clinical trials that are now accepting patients with extramedullary plasmacytoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

Yleistä tietoa kliinisistä tutkimuksista on saatavissa myös NCI verkkosivustosta.

Viitteet:

1. Tsang RW, Gospodarowicz MK, Pintilie M, et al.: Solitary plasmacytoma treated with radiotherapy: impact of tumor size on outcome. Int J Radiat Oncol Biol Phys 50 (1): 113-20, 2001.
2. Alexiou C, Kau RJ, Dietzfelbinger H, et al.: Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 85 (11): 2305-14, 1999.
3. Meis JM, Butler JJ, Osborne BM, et al.: Solitary plasmacytomas of bone and extramedullary plasmacytomas. A clinicopathologic and immunohistochemical study. Cancer 59 (8): 1475-85, 1987.
4. Soesan M, Paccagnella A, Chiarion-Sileni V, et al.: Extramedullary plasmacytoma: clinical behaviour and response to treatment. Ann Oncol 3 (1): 51-7, 1992.
5. Strojan P, Soba E, Lamovec J, et al.: Extramedullary plasmacytoma: clinical and histopathologic study. Int J Radiat Oncol Biol Phys 53 (3): 692-701, 2002.

Initial Evaluation

The initial approach to the patient is to evaluate the following parameters:

1. Detection of a monoclonal (or myeloma) protein (M protein) in the serum or urine.
2. Detection of more than 10% of plasma cells on a bone marrow examination.
3. Detection of lytic bone lesions or generalized osteoporosis in skeletal x-rays.
4. Presence of soft tissue plasmacytomas.
5. Serum albumin and beta-2-microglobulin levels.
6. Detection of free kappa and lambda serum immunoglobulin light chain.[1]

Treatment selection is influenced by the age and general health of the patient, prior therapy, and the presence of complications of the disease.[2]

Induction Therapy

The choice of induction therapy is unclear at the present time; however, the current basic categories include the use of steroids, thalidomide, and lenalidomide.

Several questions are raised when therapy is being chosen for a patient with symptomatic myeloma at first presentation, including the following:

1. Is the patient eligible for a clinical trial? The sequence and combinations of new and older therapies can only be determined by prospective clinical trials.
2. Is autologous stem cell transplantation (ASCT) a possible consolidation option for this patient? If so, alkylating agents should be avoided during induction therapy to avoid compromise of stem cell collection and to lessen leukemogenic risk.
3. Does the patient have comorbidities? Age, organ dysfunction, and risk of cardiovascular and thrombotic complications would influence the choice of induction therapies as well as the choice of whether to consider consolidation therapies.

Induction therapy agents

Multiple therapeutic agents are available for induction therapy, either alone or in combinations.[3] These include the following:

Steroids (eg, dexamethasone and prednisone).Thalidomide.Lenalidomide.Bortezomib.Alkylating agents (eg, melphalan and cyclophosphamide).Other cytotoxic drugs (eg, vincristine, doxorubicin, and liposomal doxorubicin).

Clinical trials are needed to establish the regimens with the best efficacy and least long-term toxicity. (Refer to the Combination therapy section of this summary for a list of current clinical trials.)

Guidelines for choosing induction therapy

Until results become available, outside the context of a clinical trial, clinicians may choose induction therapy based on the following guidelines:

1. In patients younger than 70 years, alkylators are avoided up front to avoid stem cell toxicity with subsequent risks for cytopenias, secondary malignancies, or poor stem cell harvesting if transplantation is considered for consolidation therapy.[4]
2. Bortezomib or lenalidomide is combined with dexamethasone for at least 8 months or until best response if consolidation therapy is planned.[5,6] (Refer to the Lenalidomide and Bortezomib sections of this summary for more information.)
3. The choice of bortezomib or lenalidomide is based on side-effect profile and route of administration.

Bortezomib is given in frequent intravenous doses and can cause significant neuropathic toxicities.[6,7,8] Bortezomib is preferred in the setting of renal impairment.[9]Lenalidomide is given orally and can cause an increased risk for deep venous thrombosis (DVT), requiring additional prophylactic medication.[5,10]
4. Patients with standard-risk disease, as defined in the Stage Information About Plasma Cell Neoplasms section of this summary, might receive induction therapy alone, followed by careful observation after best response.[11]
5. Patients with high-risk disease might receive induction therapy until best response, followed by consolidation therapy with allogeneic or ASCT.[11]

These guidelines require validation by ongoing clinical trials; participation in clinical trials is the preferred choice, when possible.

Kortikosteroidit

Since the mid-1980s, dexamethasone has been administered at a dose of 40 mg orally for 4 consecutive days, which is the same schedule used with the vincristine plus doxorubicin plus dexamethasone (VAD) regimen.[12] Response rates of 60% to 70% in previously untreated patients appeared to be as high as those in patients treated with VAD.[12,13][Level of evidence: 3iiiDiv]

Evidence:

A prospective trial randomly assigned 488 patients older than 65 years to receive dexamethasone alone, melphalan plus dexamethasone, dexamethasone plus interferon-alpha, and melphalan plus prednisone (MP).

With a median follow-up of 7.1 years, no difference was observed in overall survival (OS) (median survival times were 32 months–40 months).[14][Level of evidence: 1iiA]The patients on the dexamethasone-based arms had significantly more infections, glucose intolerance, gastrointestinal symptoms, and psychiatric complaints. (Refer to the PDQ summary on Gastrointestinal Complications for more information on gastrointestinal symptoms.)

There has never been a randomized trial comparing single-agent oral dexamethasone at a traditional high dose (40 mg a day for 4 days, repeated after 4 days off) with a lower dose (≤40 mg weekly). This issue of dexamethasone dose has been evaluated in two of the following prospective, randomized trials:

In the context of melphalan, as evaluated in a National Cancer Institute of Canada trial (CAN-NCIC-MY7).

Compared with standard-dose steroids, high-dose dexamethasone was associated with an increased risk of infection in the melphalan trial, but there was no difference in efficacy.[15]In the context of lenalidomide, as evaluated in an Eastern Cooperative Oncology Group trial (ECOG-E4A03).[5]

The lenalidomide study questioned the safety and efficacy of high-dose dexamethasone.[5] (Refer to the Lenalidomide section of this summary for more information.)

Almost all ongoing clinical trials in the United States and Europe have implemented the low-dose dexamethasone schedule with or without other therapeutic agents.

Thalidomide

Evidence:

Ten randomized prospective studies involving more than 4,500 patients have examined the introduction of thalidomide as induction therapy for previously untreated symptomatic patients with multiple myeloma.[16,17,18,19,20,21,22,23,24]

All of the trials reported improved response rates with the introduction of thalidomide and no hematopoietic damage, allowing adequate stem cell collection when applicable or allowing combinations with other myelosuppressive agents.Only two of the ten randomized studies reported a survival advantage using thalidomide. In these trials, the patients older than 65 or 75 years at the 2-year follow-ups showed a 44- to 56-month median OS for MP plus thalidomide versus 28- to 30-month median OS for MP ( P < .03 in both studies).[22,25][Level of evidence: 1iiA] A possible explanation is that these two trials used a lower dose of thalidomide than the other studies (100 mg vs. ≥200 mg), a lower dose of steroids (60 mg of prednisone vs. high-dose dexamethasone), and involved the use of alkylating agents.

As previously described in the section on corticosteroids, high-dose dexamethasone can complicate interpretation of clinical trials by worsening cardiopulmonary toxicity and deaths, especially in the context of thalidomide or lenalidomide, both of which are thrombogenic agents.

Factors that have been implicated to worsen the risk of DVT include the use of high-dose dexamethasone, concomitant erythropoietic growth factors, and concomitant doxorubicin, liposomal doxorubicin, or alkylating agents.[26,27]

Personal cardiovascular risk factors can also influence the rate of DVT. Various clinical trials have included different DVT prophylaxis measures, including aspirin (81 mg–100 mg a day), warfarin, or low molecular-weight heparin, but the validity of these measures has not been studied prospectively in a randomized study.[20,22,27,28,29]

Prospective electrophysiologic monitoring provides no clear benefit over clinical evaluation for the development of clinically significant neuropathy while on thalidomide.

Lenalidomide

Evidence:

1. A prospective randomized study of 351 relapsed patients compared lenalidomide, an analog of thalidomide, plus high-dose dexamethasone with high-dose dexamethasone plus placebo.[30]

The lenalidomide combination showed a significantly higher time to tumor progression (11.3 months vs. 4.7 months, P < .001) with a 16-month median follow-up, and median OS had not been reached, versus 20.6 months in the placebo group (hazard ratio [HR] = 0.66, 95% confidence interval [CI], 0.45–0.96, P = .03).[30][Level of evidence: 1iA]The lenalidomide-containing arm had more DVT (11.4% vs. 4.6%).[30]
2. Similarly, another randomized, prospective trial (NCT00056160) of 353 previously treated patients favored the lenalidomide plus high-dose dexamethasone arm versus dexamethasone plus placebo.

With a median follow-up of 26 months, the median time to progression was 11.1 months versus 4.7 months ( P < .001) and the median OS was 29.6 months versus 20.2 months ( P < .001).[31][Level of evidence: 1iA]
3. A prospective, randomized study (ECOG-E4A03) of 445 untreated symptomatic patients compared lenalidomide and high-dose dexamethasone (40 mg on days 1–4, 9–12, and 17–20, every 28 days) with lenalidomide and low-dose dexamethasone (40 mg on days 1, 8, 15, and 22, every 28 days).[5]

With a median follow-up of 36 months, this trial showed improved OS for patients in the low-dose dexamethasone arm (87% vs. 75% at 2 years, P = .006), despite no difference in progression-free survival (PFS).[5][Level of evidence: 1iiA]The extra deaths on the high-dose dexamethasone arm were attributed to cardiopulmonary toxicity and faster progression with subsequent therapies. DVTs were also more frequent in the high-dose arm (25% vs. 9%).OS favored the low-dose arm with a 2-year survival of 87% versus 75% in the high-dose arm ( P = .006).[5][Level of evidence: 1iiA] The low-dose dexamethasone arm with lenalidomide had less than 5% DVT with aspirin alone.
4. A retrospective analysis of 353 patients who received lenalidomide and high-dose dexamethasone found that the 17% of the patients who experienced a thromboembolic episode had no decrease in OS or time to progression.[32][Level of evidence: 3iiiA]

Lenalidomide has substantially greater myelosuppression but less neuropathy than seen with thalidomide; however, both have the same tendency for DVT.[5,30,31,32] DVT prophylaxis with 81 mg of aspirin has been proposed, but randomized clinical trials have not confirmed any benefit for this recommendation.[29] Empirically, the greater the number of risk factors for DVT, the more intense the recommendation for prophylactic anticoagulation. (Refer to the Thalidomide section of this summary for more information about risk factors.) As a result of predominant renal clearance, lenalidomide doses need to be reduced in the setting of impaired renal function (creatinine clearance, 30–50: 10 mg per day; creatinine clearance, <30: 15 mg every other day; dialysis, 15 mg on day after dialysis).[33]

Bortezomib

Evidence:

1. A prospective randomized trial (NCT00111319) of 682 previously untreated symptomatic patients who were not candidates for stem cell transplantation because of age (one-third of patients >75 years) compared bortezomib combined with melphalan and prednisone with melphalan and prednisone alone.[6]

With a median follow-up of 37 months, the OS favored the bortezomib arm in the 3-year OS rates (69% vs. 54%, P = .03).[6][Level of evidence: 1iiA]
2. A prospective randomized study of 669 patients with relapsing myeloma, who had been treated previously with steroids, compared intravenous bortezomib with high-dose oral dexamethasone.

With a median follow-up of 22 months, the median OS was 29.8 months for bortezomib versus 23.7 months for dexamethasone (HR = 0.77, P = .027), despite 62% of dexamethasone patients crossing over to receive bortezomib.[7][Level of evidence: 1iiA]Bortezomib-associated peripheral neuropathy is reversible in most patients after dose reduction or discontinuation.[8,34,35,36,37]
3. A prospective, randomized trial (NCT00103506) of 646 previously treated patients compared bortezomib plus pegylated liposomal doxorubicin with bortezomib alone.[38]

With a median follow-up of 7 months, the combination was better in both median time to progression (9.3 months vs. 6.5 months, P < .001) and in OS (82% vs. 75%, P = .05).[38][Level of evidence: 1iiA]

When bortezomib was incorporated with induction therapy, patients with unfavorable molecular cytogenetics did not show any difference in PFS or OS compared with patients with more favorable risk factors. The benefit from bortezomib appears to be maintained across risk groups, but not reproducibly in all studies.[39,40,41,42,43][Level of evidence: 3iiiD]

Because bortezomib is metabolized and cleared by the liver, it appears active and well tolerated in patients with renal impairment.[9,44,45] In a retrospective, nonrandomized comparison, bortezomib administered once weekly had significantly less grade 3 to 4 peripheral neuropathy (8% vs. 28%, P < .001) with no loss of efficacy compared with standard biweekly administration.[46]

Conventional-dose chemotherapy

Evidence:

The VAD regimen has shown activity in previously treated and in untreated patients with response rates ranging from 60% to 80%.[47,48,49,50][Level of evidence: 3iiiDiv]

No randomized studies support the widespread use of this regimen in untreated patients.This regimen avoids early exposure to alkylating agents, thereby minimizing any problems with stem cell collection (if needed) and any future risks for myelodysplasia or secondary leukemia.Disadvantages include the logistics for a 96-hour infusion of doxorubicin and a low complete response rate.An alternative version of VAD substitutes pegylated liposomal doxorubicin for doxorubicin, eliminates the need for an infusion, and provides comparable response rates.[51,52][Level of evidence: 3iiiDiv]

Evidence is not strong that any alkylating agent is superior to any other. All standard doses and schedules produce equivalent results.[53] The two most common regimens historically have been oral MP and oral cyclophosphamide plus prednisone.[53,54,55]

Combinations, such as those used in EST-2479, of alkylating agents and prednisone, administered simultaneously or alternately, have not proven to be superior to therapy with MP.[56,57,58,59][Level of evidence: 1iiA]

A meta-analysis of studies comparing MP with drug combinations concluded that both forms of treatment were equally effective.[53][Level of evidence: 1iiA] Patients who relapsed after initial therapy with cyclophosphamide and prednisone had no difference in OS (median OS, 17 months) when randomly assigned to receive vincristine plus carmustine plus melphalan plus cyclophosphamide plus prednisone or VAD.[60][Level of evidence: 1iiA]

Combination therapy

Evidence:

Several national and international trials have been implemented to define the optimal combination regimens. Participation in these trials should be the preferred approach, when feasible. The combination regimens in these trials represent the most successful from numerous phase II reports during the last several years.

ECOG-E1A05: Bortezomib + dexamethasone versus lenalidomide + bortezomib + dexamethasone.[61]SWOG-S0777: Lenalidomide + dexamethasone versus lenalidomide + bortezomib + dexamethasone.EVOLUTION (NCT00507442) trial: Bortezomib + lenalidomide + dexamethasone versus bortezomib + cyclophosphamide + dexamethasone versus bortezomib + lenalidomide + cyclophosphamide + dexamethasone.US Intergroup/Intergroupe Francais du Myélome trial (IFM): Lenalidomide + bortezomib + dexamethasone for three cycles; responders are then randomly assigned to five more cycles of lenalidomide + bortezomib + dexamethasone or high-dose melphalan + stem cell transplantation.ECOG-E1A06: Thalidomide + melphalan + prednisone versus lenalidomide + melphalan + prednisone.

Options for combination regimens:

1. Bortezomib + dexamethasone (as demonstrated in ECOG-E1A05).[39,61]
2. Lenalidomide + dexamethasone (as demonstrated in SWOG-S0777).[5,30,31]
3. Bortezomib + lenalidomide + dexamethasone (as demonstrated in ECOG-E1A05, SWOG-S0777, EVOLUTION trial, and the US Intergroup/IFM trial).[39,61,62]
4. Bortezomib + cyclophosphamide + dexamethasone (as demonstrated in the EVOLUTION trial).[63,64]
5. Bortezomib + lenalidomide + cyclophosphamide + dexamethasone (as demonstrated in the EVOLUTION trial).[65]
6. Lenalidomide + cyclophosphamide + dexamethasone.[66]
7. Bortezomib + melphalan + prednisone.[6]
8. Bortezomib + liposomal doxorubicin +/- dexamethasone.[38,67]
9. Melphalan + prednisone + thalidomide.[18,25]
10. Melphalan + prednisone.[18,25]

Consolidation Chemotherapy

High-dose chemotherapy: Autologous bone marrow or peripheral stem cell transplantation

Evidence:

The failure of conventional therapy to cure the disease has led investigators to test the effectiveness of much higher doses of drugs such as melphalan. The development of techniques for harvesting hemopoietic stem cells, from marrow aspirates or the peripheral blood of the patient, and infusing these cells to promote hemopoietic recovery made it possible for investigators to test very large doses of chemotherapy.

Based on the experience of treating thousands of patients in this way, it is possible to draw a few conclusions, including the following:

The risk of early death caused by treatment-related toxic effects has been reduced to less than 3% in highly selected populations.[68]Chemotherapy patients can now be treated as outpatients.Extensive prior chemotherapy, especially with alkylating agents, compromises marrow hemopoiesis and may make the harvesting of adequate numbers of hemopoietic stem cells impossible.[4]Younger patients in good health tolerate high-dose therapy better than patients with a poor performance status.[69,70,71]Upon review of eight updated trials encompassing more than 3,100 patients, at 10 years' follow-up, there was a 10% to 35% event-free survival (EFS) rate and a 20% to 50% OS rate.[72]

Single autologous bone marrow or peripheral stem cell transplantation

Evidence:

While some prospective randomized trials, such as the US Intergroup trial SWOG-9321, have shown improved survival for patients who received autologous peripheral stem cell or bone marrow transplantation after induction chemotherapy versus chemotherapy alone,[73,74,75][Level of evidence: 1iiA] other trials have not shown any survival advantage.[76,77,78,79][Level of evidence: 1iiA]

Two meta-analyses of almost 3,000 patients showed no survival advantage.[80,81][Level of evidence: 1iiA]

Even the trials suggesting improved survival showed no signs of a slowing in the relapse rate or a plateau to suggest that any of these patients had been cured.[73,74,75,82] The role of ASCT has also been questioned with the advent of novel induction therapies with high complete-remission rates.[83,84]

Tandem autologous bone marrow or peripheral stem cell transplantation

Another approach to high-dose therapy has been the use of two sequential episodes of high-dose therapy with stem cell support (tandem transplants).[85,86,87,88,89]

Evidence:

1. A meta-analysis of six randomized clinical trials enrolling 1,803 patients compared single autologous hematopoietic cell transplantation with tandem autologous hematopoietic cell transplantation.

There was no difference in OS (HR = 0.94; 95% CI, 0.77–1.14) or in EFS (HR = 0.86; 95% CI, 0.70–1.05).[90][Level of evidence: 1A]
2. In a trial of 194 previously untreated patients aged 50 to 70 years, the patients were randomly assigned to either conventional oral melphalan and prednisone or VAD for two cycles followed by two sequential episodes of high-dose therapy (melphalan 100 mg/m 2 ) with stem cell support.[75]

With a median follow-up of more than 3 years, the double transplant group had superior EFS (37% vs. 16% at 3 years, P < .001) and OS (77% vs. 62%, P < .001).[75][Level of evidence: 1iiA]
3. Three different groups have compared two tandem autologous transplants with one autologous transplant followed by a reduced-intensity conditioning allograft from an HLA-identical sibling; treatment assignment was based on the presence or absence of an HLA-identical sibling. The results have been discordant for survival in these nonrandomized trials.

One study showed a survival advantage for the two tandem autologous transplants.One study showed a survival advantage for the autologous transplant followed by an allogeneic transplant.One study showed no difference in OS.[91,92,93,94][Level of evidence: 3iiiA]With a median follow-up of 45 months, the median OS was 54 months for the tandem autologous grafts versus 80 months for the allogeneic graft ( P = .01).[91][Level of evidence: 3iiA]
4. A trial of 195 patients younger than 60 years with newly diagnosed myeloma randomly compared two tandem transplants with a single autologous stem cell transplant followed by 6 months of maintenance therapy with thalidomide.

With a median follow-up of 33 months, the thalidomide maintenance arm showed a benefit in PFS (85% vs. 57% at 3 years, P = .02) and OS (85% vs. 65% at 3 years, P = .04).[95][Level of evidence: 1iiA]

High-dose chemotherapy: Allogeneic bone marrow or peripheral stem cell transplantation

Evidence:

In a registry of 162 patients who underwent allogeneic matched sibling-donor transplants, the actuarial OS rate was 28% at 7 years.[96][Level of evidence: 3iiiA]

Favorable prognostic features included the following:

Low tumor burden.Responsive disease before transplant.Application of transplantation after first-line therapy.

Many patients are not young enough or healthy enough to undergo these intensive approaches. A definite graft-versus-myeloma effect has been demonstrated, including regression of myeloma relapses following the infusion of donor lymphocytes.[97,98,99,100]

Myeloablative allogeneic stem cell transplantation has significant toxic effects (15%–40% mortality), but the possibility of a potent and possibly curative graft-versus-myeloma effect in a minority of patients may offset the high transplant-related mortality.[100,101,102]

Further research is required to make allogeneic transplants less dangerous and to find methods for initiating an autoimmune response to the myeloma cells. Nonmyeloablative allogeneic stem cell transplant is under development.[103,104,105] Such strategies aim to maintain efficacy (so called graft-versus-tumor effect) while reducing transplant-related mortality.[106,107] The lower transplant-related mortality from nonmyeloablative approaches has been accompanied by a greater risk of relapse.[102] Given the lack of evidence so far that the high-risk patients benefit from allogeneic stem cell transplantation in this era of novel new agents, it remains debatable whether allogeneic stem cell transplantation should be offered in the first-line setting outside the context of a clinical trial.[102]

Maintenance Therapy

Clinical trials exploring thalidomide as maintenance therapy have contradictory results.

Myeloma patients who respond to treatment show a progressive fall in the M protein until a plateau is reached; subsequent treatment with conventional doses does not result in any further improvement. This has led investigators to question how long treatment should be continued.

Evidence:

1. In a single study,[108] it was observed that maintenance therapy with MP prolonged the initial remission duration (31 months) compared with no maintenance treatment (23 months).

No effect on OS was found because the majority of patients who relapsed in the no maintenance arm responded again to MP, while those on maintenance MP did not respond to further treatment.The Canadian group [108] suggests that induction chemotherapy be continued as long as the M protein continues to fall; therapy can be discontinued after the M protein reaches a plateau that remains stable for 4 months.
2. Maintenance interferon-alpha therapy has been reported in several studies to prolong initial remission duration after conventional chemotherapy.[109,110,111,112] While the impact of interferon maintenance on disease-free survival and OS has significantly varied among trials, a meta-analysis of 1,543 patients treated on 12 trials randomizing between interferon maintenance and observation indicated that interferon maintenance was associated with improved relapse-free survival (27% vs. 19% at 3 years, P < .001) and OS (12% odds reduction, P = .04).[113] Toxic effects in this population may be substantial and must be balanced against the potential benefits in response duration.[114]
3. A randomized study compared maintenance interferon with maintenance thalidomide in 103 previously untreated and treated patients who had at least a minimal response to induction chemotherapy with thalidomide, pegylated liposomal doxorubicin, and dexamethasone. With a median follow-up of 30 months, the thalidomide maintenance arm was better, with 2-year PFS of 63% versus 32% ( P = .024) and a 2-year OS of 84% versus 68% ( P = .03).[115][Level of evidence: 1iiA]
4. In a trial of 556 previously untreated patients induced with thalidomide, doxorubicin, dexamethasone, and followed by high-dose melphalan with stem cell support, patients were randomly assigned to alpha interferon or to thalidomide maintenance. With a median follow-up of 52 months, there was no significant difference in median survival ( P = .77) 60 months for interferon and 73 months for thalidomide.[24][Level of evidence: 1iiA]
5. Maintenance therapy with interferon showed a benefit in PFS (46 months vs. 27 months, P < .025) and OS (75% vs. 50%, P < .01) in a randomized study of 84 patients following autologous bone marrow transplantation.[116][Level of evidence: 1iiA] A larger randomized trial of 805 patients showed no difference in PFS or OS with interferon given after peripheral stem cell transplantation or conventional chemotherapy.[117][Level of evidence: 1iiA]
6. In a randomized trial, 269 patients with newly diagnosed myeloma were given maintenance thalidomide plus prednisolone versus prednisolone alone following both induction therapy and high-dose melphalan with ASCT. The trial showed a benefit in favor of the thalidomide arm after a median follow-up of 3 years: 3-year PFS, 43% versus 23% ( P < .001); 3-year OS, 86% versus 75% ( P = .004).[118][Level of evidence: 1iiA] As a result of these varying outcomes, further clinical trial results are required to determine whether there is a benefit of maintenance therapy.
7. A study of 125 responding patients with first-line VAD induction who were randomly assigned to maintenance corticosteroids at 10 mg or 50 mg on alternate days showed improved PFS (14 months vs. 5 months, P = .003) and OS (36 months vs. 26 months, P = .05) for the patients receiving the higher-dose corticosteroids.[119][Level of evidence: 1iiA]
8. In a larger trial by the National Cancer Institute of Canada (CAN-NCIC-MY7) of 585 patients treated with first-line MP, 292 patients were randomly assigned to pulse dexamethasone (40 mg a day for 4 days monthly) versus no maintenance.

PFS favored the dexamethasone maintenance arm (2.8 years vs. 2.1 years, P = .002), but there was no difference in OS (4.1 years vs. 3.8 years, P = .4).[15][Level of evidence: 1iiDiii]
9. Two months after autologous transplantation, 597 patients younger than 65 years were randomly assigned to no maintenance, pamidronate, or pamidronate plus thalidomide.

The thalidomide arm was favored by EFS (36% vs. 37% vs. 52%, P < .009) and by OS at 4 years (77% vs. 74% vs. 87%, P < .04), while no differences were seen for skeletal events.[120][Level of evidence: 1iiA]
10. After autologous transplantation, 129 patients were randomly assigned to indefinite prednisone versus indefinite prednisone with 12 months of thalidomide.

With a median follow-up of 3 years, the thalidomide arm was favored by PFS (42% vs. 23%, P < .001) and by OS at 3 years (86% vs. 75%, P = .004).[118][Level of evidence: 1iiA]

Tukihoito

Bisphosphonate therapy

Evidence:

1. A randomized, double-blind study of patients with stage III myeloma showed that monthly intravenous pamidronate significantly reduced pathologic fractures, bone pain, spinal cord compression, and the need for bone radiation therapy (38% skeletal-related events were reported in the treatment group vs. 51% in the placebo group after 21 months of therapy, P = .015).[121][Level of evidence: 1iDiii] (Refer to the PDQ summary on Pain for more information on bisphosphonate therapy.)
2. A randomized comparison of pamidronate versus zoledronic acid in 518 patients with multiple myeloma showed equivalent efficacy in regard to skeletal-related complications.[122][Level of evidence: 1iDiii]

Bisphosphonates are associated with infrequent long-term complications (in 3%–5% of patients), including osteonecrosis of the jaw and avascular necrosis of the hip.[123,124] (Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information on osteonecrosis of the jaw.) These side effects must be balanced against the potential benefits of bisphosphonates when bone metastases are evident.[125] The optimal use and duration of bisphosphonates for bony involvement in myeloma have not been studied. Bisphosphonates are usually given intravenously on a monthly basis for 2 years and then extended at the same schedule or at a reduced schedule (ie, once every 3–4 months), if there is evidence of active myeloma bone disease.[67,126]

3. A double-blind, randomized, controlled trial with 504 patients with newly diagnosed multiple myeloma compared 30 mg of pamidronate to 90 mg of pamidronate and found there was no difference in skeletal-related events, but there was less osteonecrosis (2 events vs. 8 events) seen in the low-dose group.[127][Level of evidence: 1iDiv]

Bone lesions

Lytic lesions of the spine should be radiated if any of the following are true:

If they are associated with an extramedullary (paraspinal) plasmacytoma.If a painful destruction of a vertebral body occurred.If computed tomography or MRI scans present evidence of spinal cord compression.[128]

Back pain caused by osteoporosis and small compression fractures of the vertebrae responds best to chemotherapy. (Refer to the PDQ summary on Pain for more information on back pain.)

Extensive radiation of the spine or long bones for diffuse osteoporosis may lead to prolonged suppression of hemopoiesis and is rarely indicated.[129]

Bisphosphonates are useful for slowing or reversing the osteopenia that is common in myeloma patients.[121]

Nykyinen kliinisiä tutkimuksia

Check for US clinical trials from NCI's list of cancer clinical trials that are now accepting patients with multiple myeloma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

Yleistä tietoa kliinisistä tutkimuksista on saatavissa myös NCI verkkosivustosta.

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47. Alexanian R, Barlogie B, Tucker S: VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 33 (2): 86-9, 1990.
48. Segeren CM, Sonneveld P, van der Holt B, et al.: Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma. Br J Haematol 105 (1): 127-30, 1999.
49. Anderson H, Scarffe JH, Ranson M, et al.: VAD chemotherapy as remission induction for multiple myeloma. Br J Cancer 71 (2): 326-30, 1995.
50. Browman GP, Belch A, Skillings J, et al.: Modified adriamycin-vincristine-dexamethasone (m-VAD) in primary refractory and relapsed plasma cell myeloma: an NCI (Canada) pilot study. The National Cancer Institute of Canada Clinical Trials Group. Br J Haematol 82 (3): 555-9, 1992.
51. Dimopoulos MA, Pouli A, Zervas K, et al.: Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma. Ann Oncol 14 (7): 1039-44, 2003.
52. Rifkin RM, Gregory SA, Mohrbacher A, et al.: Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial. Cancer 106 (4): 848-58, 2006.
53. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Myeloma Trialists' Collaborative Group. J Clin Oncol 16 (12): 3832-42, 1998.
54. Gregory WM, Richards MA, Malpas JS: Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol 10 (2): 334-42, 1992.
55. Bergsagel DE, Stewart AK: Conventional-dose chemotherapy of myeloma. In: Malpas JS, Bergsagel DE, Kyle RA, et al.: Myeloma: Biology and Management. 3. painos. Philadelphia, Pa: WB Saunders Co, 2004, pp 203-17.
56. Pavlovsky S, Corrado C, Santarelli MT, et al.: An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study. J Clin Oncol 6 (5): 769-75, 1988.
57. Bladé J, San Miguel JF, Alcalá A, et al.: Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients. J Clin Oncol 11 (6): 1165-71, 1993.
58. Oken MM, Harrington DP, Abramson N, et al.: Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479. Cancer 79 (8): 1561-7, 1997.
59. Gertz MA, Lacy MQ, Lust JA, et al.: Prospective randomized trial of melphalan and prednisone versus vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis. J Clin Oncol 17 (1): 262-7, 1999.
60. Mineur P, Ménard JF, Le Loët X, et al.: VAD or VMBCP in multiple myeloma refractory to or relapsing after cyclophosphamide-prednisone therapy (protocol MY 85). Br J Haematol 103 (2): 512-7, 1998.
61. Fonseca R, Rajkumar SV: Consolidation therapy with bortezomib/lenalidomide/ dexamethasone versus bortezomib/dexamethasone after a dexamethasone-based induction regimen in patients with multiple myeloma: a randomized phase III trial. Clin Lymphoma Myeloma 8 (5): 315-7, 2008.
62. Richardson P, Lonial S, Jakubowiak A, et al.: Lenalidomide, bortezomib, and dexamethasone in patients with newly diagnosed multiple myeloma: encouraging efficacy in high risk groups with updated results of a phaseI/II study. [Abstract] Blood 112 (11): A-92, 2008.
63. Reece DE, Rodriguez GP, Chen C, et al.: Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma. J Clin Oncol 26 (29): 4777-83, 2008.
64. Knop S, Liebisch H, Wandt H, et al.: Bortezomib, IV cyclophosphamide, and dexamethasone (VelCD) as induction therapy in newly diagnosed multiple myeloma: results of an interim analysis of the German DSMM Xia trial. [Abstract] J Clin Oncol 27 (Suppl 15): A-8516, 2009.
65. Kumar S, Flinn IW, Noga SJ, et al.: Safety and efficacy of novel combination therapy with bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in newly diagnosed multiple myeloma: initial results from the phase I/II multi-center EVOLUTION study. [Abstract] Blood 112 (11): A-93, 2008.
66. Kumar S, Hayman S, Buadi F, et al.: Phase II trial of lenalidomide (Revlimid™) with cyclophosphamide and dexamethasone (RCd) for newly diagnosed myeloma. [Abstract] Blood 112 (11): A-91, 2008.
67. Jakubowiak AJ, Kendall T, Al-Zoubi A, et al.: Phase II trial of combination therapy with bortezomib, pegylated liposomal doxorubicin, and dexamethasone in patients with newly diagnosed myeloma. J Clin Oncol 27 (30): 5015-22, 2009.
68. Bladé J, Vesole DH, Gertz Morie: High-dose therapy in multiple myeloma. Blood 102 (10): 3469-70, 2003.
69. Siegel DS, Desikan KR, Mehta J, et al.: Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 93 (1): 51-4, 1999.
70. Badros A, Barlogie B, Siegel E, et al.: Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol 114 (3): 600-7, 2001.
71. Lenhoff S, Hjorth M, Westin J, et al.: Impact of age on survival after intensive therapy for multiple myeloma: a population-based study by the Nordic Myeloma Study Group. Br J Haematol 133 (4): 389-96, 2006.
72. Barlogie B, Attal M, Crowley J, et al.: Long-term follow-up of autotransplantation trials for multiple myeloma: update of protocols conducted by the intergroupe francophone du myelome, southwest oncology group, and university of arkansas for medical sciences. J Clin Oncol 28 (7): 1209-14, 2010.
73. Attal M, Harousseau JL, Stoppa AM, et al.: A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med 335 (2): 91-7, 1996.
74. Child JA, Morgan GJ, Davies FE, et al.: High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348 (19): 1875-83, 2003.
75. Palumbo A, Bringhen S, Petrucci MT, et al.: Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood 104 (10): 3052-7, 2004.
76. Segeren CM, Sonneveld P, van der Holt B, et al.: Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study. Blood 101 (6): 2144-51, 2003.
77. Fermand JP, Katsahian S, Divine M, et al.: High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 23 (36): 9227-33, 2005.
78. Bladé J, Rosiñol L, Sureda A, et al.: High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood 106 (12): 3755-9, 2005.
79. Barlogie B, Kyle RA, Anderson KC, et al.: Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol 24 (6): 929-36, 2006.
80. Lévy V, Katsahian S, Fermand JP, et al.: A meta-analysis on data from 575 patients with multiple myeloma randomly assigned to either high-dose therapy or conventional therapy. Medicine (Baltimore) 84 (4): 250-60, 2005.
81. Koreth J, Cutler CS, Djulbegovic B, et al.: High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. Biol Blood Marrow Transplant 13 (2): 183-96, 2007.
82. Pineda-Roman M, Barlogie B, Anaissie E, et al.: High-dose melphalan-based autotransplants for multiple myeloma: the Arkansas experience since 1989 in 3077 patients. Cancer 112 (8): 1754-64, 2008.
83. Giralt S, Stadtmauer EA, Harousseau JL, et al.: International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia 23 (10): 1904-12, 2009.
84. Harousseau JL: Hematopoietic stem cell transplantation in multiple myeloma. J Natl Compr Canc Netw 7 (9): 961-70, 2009.
85. Barlogie B, Tricot GJ, van Rhee F, et al.: Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 135 (2): 158-64, 2006.
86. Barlogie B, Tricot G, Rasmussen E, et al.: Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies. Blood 107 (7): 2633-8, 2006.
87. Barlogie B, Zangari M, Bolejack V, et al.: Superior 12-year survival after at least 4-year continuous remission with tandem transplantations for multiple myeloma. Clin Lymphoma Myeloma 6 (6): 469-74, 2006.
88. Bruno B, Rotta M, Patriarca F, et al.: Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo. Blood 113 (14): 3375-82, 2009.
89. Rotta M, Storer BE, Sahebi F, et al.: Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting. Blood 113 (14): 3383-91, 2009.
90. Kumar A, Kharfan-Dabaja MA, Glasmacher A, et al.: Tandem versus single autologous hematopoietic cell transplantation for the treatment of multiple myeloma: a systematic review and meta-analysis. J Natl Cancer Inst 101 (2): 100-6, 2009.
91. Bruno B, Rotta M, Patriarca F, et al.: A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 356 (11): 1110-20, 2007.
92. Garban F, Attal M, Michallet M, et al.: Prospective comparison of autologous stem cell transplantation followed by dose-reduced allograft (IFM99-03 trial) with tandem autologous stem cell transplantation (IFM99-04 trial) in high-risk de novo multiple myeloma. Blood 107 (9): 3474-80, 2006.
93. Moreau P, Garban F, Attal M, et al.: Long-term follow-up results of IFM99-03 and IFM99-04 trials comparing nonmyeloablative allotransplantation with autologous transplantation in high-risk de novo multiple myeloma. Blood 112 (9): 3914-5, 2008.
94. Rosiñol L, Pérez-Simón JA, Sureda A, et al.: A prospective PETHEMA study of tandem autologous transplantation versus autograft followed by reduced-intensity conditioning allogeneic transplantation in newly diagnosed multiple myeloma. Blood 112 (9): 3591-3, 2008.
95. Abdelkefi A, Ladeb S, Torjman L, et al.: Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood 111 (4): 1805-10, 2008.
96. Gahrton G, Tura S, Ljungman P, et al.: Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol 13 (6): 1312-22, 1995.
97. Tricot G, Vesole DH, Jagannath S, et al.: Graft-versus-myeloma effect: proof of principle. Blood 87 (3): 1196-8, 1996.
98. Verdonck LF, Lokhorst HM, Dekker AW, et al.: Graft-versus-myeloma effect in two cases. Lancet 347 (9004): 800-1, 1996.
99. Lokhorst HM, Schattenberg A, Cornelissen JJ, et al.: Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol 18 (16): 3031-7, 2000.
100. Reynolds C, Ratanatharathorn V, Adams P, et al.: Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma. Bone Marrow Transplant 27 (8): 801-7, 2001.
101. Arora M, McGlave PB, Burns LJ, et al.: Results of autologous and allogeneic hematopoietic cell transplant therapy for multiple myeloma. Bone Marrow Transplant 35 (12): 1133-40, 2005.
102. Lokhorst H, Einsele H, Vesole D, et al.: International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol 28 (29): 4521-30, 2010.
103. Einsele H, Schäfer HJ, Hebart H, et al.: Follow-up of patients with progressive multiple myeloma undergoing allografts after reduced-intensity conditioning. Br J Haematol 121 (3): 411-8, 2003.
104. Maloney DG, Molina AJ, Sahebi F, et al.: Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 102 (9): 3447-54, 2003.
105. Badros A, Barlogie B, Morris C, et al.: High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions. Blood 97 (9): 2574-9, 2001.
106. Crawley C, Lalancette M, Szydlo R, et al.: Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. Blood 105 (11): 4532-9, 2005.
107. Badros A, Barlogie B, Siegel E, et al.: Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning. J Clin Oncol 20 (5): 1295-303, 2002.
108. Belch A, Shelley W, Bergsagel D, et al.: A randomized trial of maintenance versus no maintenance melphalan and prednisone in responding multiple myeloma patients. Br J Cancer 57 (1): 94-9, 1988.
109. Mandelli F, Avvisati G, Amadori S, et al.: Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 322 (20): 1430-4, 1990.
110. Westin J, Rödjer S, Turesson I, et al.: Interferon alfa-2b versus no maintenance therapy during the plateau phase in multiple myeloma: a randomized study. Cooperative Study Group. Br J Haematol 89 (3): 561-8, 1995.
111. Osterborg A, Björkholm M, Björeman M, et al.: Natural interferon-alpha in combination with melphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study from the Myeloma Group of Central Sweden. Blood 81 (6): 1428-34, 1993.
112. Browman GP, Bergsagel D, Sicheri D, et al.: Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 13 (9): 2354-60, 1995.
113. The Myeloma Trialists' Collaborative Group.: Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol 113 (4): 1020-34, 2001.
114. Zee B, Cole B, Li T, et al.: Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma. J Clin Oncol 16 (8): 2834-9, 1998.
115. Offidani M, Corvatta L, Polloni C, et al.: Thalidomide-dexamethasone versus interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study. Br J Haematol 144 (5): 653-9, 2009.
116. Cunningham D, Powles R, Malpas J, et al.: A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. Br J Haematol 102 (2): 495-502, 1998.
117. Barlogie B, Kyle R, Anderson K, et al.: Comparable survival in multiple myeloma (MM) with high dose therapy (HDT) employing MEL 140 mg/m2 + TBI 12 Gy autotransplants versus standard dose therapy with VBMCP and no benefit from interferon (IFN) maintenance: results of Intergroup Trial S9321. [Abstract] Blood 102 (11): A-135, 2003.
118. Spencer A, Prince HM, Roberts AW, et al.: Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 27 (11): 1788-93, 2009.
119. Berenson JR, Crowley JJ, Grogan TM, et al.: Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 99 (9): 3163-8, 2002.
120. Attal M, Harousseau JL, Leyvraz S, et al.: Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 108 (10): 3289-94, 2006.
121. Berenson JR, Lichtenstein A, Porter L, et al.: Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 16 (2): 593-602, 1998.
122. Rosen LS, Gordon D, Kaminski M, et al.: Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 98 (8): 1735-44, 2003.
123. Badros A, Weikel D, Salama A, et al.: Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 24 (6): 945-52, 2006.
124. Kademani D, Koka S, Lacy MQ, et al.: Primary surgical therapy for osteonecrosis of the jaw secondary to bisphosphonate therapy. Mayo Clin Proc 81 (8): 1100-3, 2006.
125. Lacy MQ, Dispenzieri A, Gertz MA, et al.: Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc 81 (8): 1047-53, 2006.
126. Terpos E, Sezer O, Croucher PI, et al.: The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Ann Oncol 20 (8): 1303-17, 2009.
127. Gimsing P, Carlson K, Turesson I, et al.: Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial. Lancet Oncol 11 (10): 973-82, 2010.
128. Rades D, Hoskin PJ, Stalpers LJ, et al.: Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys 64 (5): 1452-7, 2006.
129. Catell D, Kogen Z, Donahue B, et al.: Multiple myeloma of an extremity: must the entire bone be treated? Int J Radiat Oncol Biol Phys 40 (1): 117-9, 1998.

There are two main types of refractory myeloma patients:

Primary refractory patients who never achieve a response and progress while still on induction chemotherapy.Secondary refractory patients who do respond to induction chemotherapy but do not respond to treatment after relapse.

A subgroup of patients who do not achieve a response to induction chemotherapy have stable disease and enjoy a survival prognosis that is as good as that for responding patients.[1,2] When the stable nature of the disease becomes established, these types of patients can discontinue therapy until the myeloma begins to progress again. Others with primary refractory myeloma and progressive disease require a change in therapy. (Refer to the Treatment for Multiple Myeloma section of this summary for more information.)

The myeloma growth rate, as measured by the monoclonal (or myeloma) protein-doubling time, for patients who respond to their initial therapy increases progressively with each subsequent relapse, and remission durations become shorter and shorter. Marrow function becomes increasingly compromised as patients develop pancytopenia and enter a refractory phase; occasionally, the myeloma cells dedifferentiate and extramedullary plasmacytomas develop. The myeloma cells may still be sensitive to chemotherapy, but the regrowth rate during relapse is so rapid that progressive improvement is not observed.

Nykyinen kliinisiä tutkimuksia

Check for US clinical trials from NCI's list of cancer clinical trials that are now accepting patients with refractory multiple myeloma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

Yleistä tietoa kliinisistä tutkimuksista on saatavissa myös NCI verkkosivustosta.

Viitteet:

1. Riccardi A, Mora O, Tinelli C, et al.: Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol. Eur J Cancer 39 (1): 31-7, 2003.
2. Durie BG, Jacobson J, Barlogie B, et al.: Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials. J Clin Oncol 22 (10): 1857-63, 2004.

PDQ syöpä yhteenvetoja tarkistetaan säännöllisesti ja päivitetään kun uutta tietoa tulee saataville. Tässä osassa kuvataan viimeisimmät muutokset tähän yhteenvedon siitä päivästä, jona edellä.

General Information About Plasma Cell Neoplasms

Päivitetty tilastojen kanssa arvioitu uutta tapausta ja kuolemia 2012 (mainittu American Cancer Society referenssinä 1).

Revised text in Table 1 under clinical presentation to include asymptomatic for isolated plasmacytoma of bone and extramedullary plasmacytoma.

Added Bird et al. as reference 18.

Stage Information About Plasma Cell Neoplasms

Added Kumar et al. as reference 7.

Added text to state that plasma cell leukemia has a particularly poor prognosis (cited Ramsingh et al. as reference 8).

Treatment Option Overview for Plasma Cell Neoplasms

Added text to state that increasing anemia is the most reliable indicator of progression (cited Bladé et al. as reference 4).

Treatment for Amyloidosis Associated With Plasma Cell Neoplasms

Added text about the Southwest Oncology Group trial for dexamethasone alone and in combination, and added melphalan and bortezomib as treatments combined with thalidomide, cyclophosphamide, and lenalidomide (cited Kastritis et al. as reference 7 and Moreau et al. as reference 8).

Treatment for Monoclonal Gammopathy of Undetermined Significance (MGUS)

Added text to state that new therapies have not been proven to prevent or delay the progression of MGUS to a plasma cell dyscrasia (cited Bird et al. as reference 2).

Added Bladé et al. as reference 3.

Treatment for Multiple Myeloma

Added Raab et al. as reference 2.

Added Rajkumar et al. and Mateos et al. as references 5 and 6, respectively.

Added Bladé et al. as reference 10.

Added Kumar et al. as reference 11.

Revised text to state that there were ten randomized prospective studies involving more than 4,500 patients that examined the introduction of thalidomide as induction therapy (cited Cavo et al. as reference 23 and Lokhorst et al. as reference 24).

Revised text to state that only two of the ten randomized studies reported a survival advantage using thalidomide, and the patients in these trials were older than 65 or 75 years.

Revised text to state that a lower dose of thalidomide and a lower dose of steroids were administered than in the other studies.

Added Weber et al. as reference 27.

Revised text to state that with a median follow-up of 36 months, the Eastern Cooperative Oncology Group's (ECOG) E4A03 trial showed improved overall survival (OS) for patients in the low-dose dexamethasone arm.

Added text about a retrospective analysis of 353 patients who received lenalidomide and high-dose dexamethasone (cited Zangari et al. as reference 32 and level of evidence 3iiiA).

Added text to state that the greater the number of risk factors for deep vein thrombosis, the more intense the recommendation for prophylactic anticoagulation; also, as a result of predominant renal clearance, lenalidomide doses need to be reduced in the setting of impaired renal function (cited 2010 Dimopoulos et al. as reference 33).

Added Richardson et al. as reference 37.

Revised text to state that the benefit from bortezomib appears to be maintained across risk groups but not reproducibly in all studies (cited Avet-Loiseau et al. as reference 43).

Added 2009 Dimopoulos et al. and Morabito et al. as references 44 and 45, respectively.

Added text to state that bortezomib administered once weekly had less grade 3 to 4 peripheral neuropathy with no loss of efficacy compared with standard biweekly administration (cited Bringhen et al. as reference 46).

Added text to the list of trials of combination regimens to include ECOG-E1A06: Thalidomide + melphalan + prednisone versus lenalidomide + melphalan + prednisone.

Revised text in the options for combination regimens to include bortezomib + liposomal doxorubicin +/- dexamethasone (cited Jakubowiak et al. as reference 67).

Added text to state that upon review of eight updated trials encompassing more than 3,100 patients, at 10 years' follow-up, there was a 10% to 35% event-free survival rate and a 20% to 50% OS rate (cited Barlogie et al. as reference 72).

Added text to state that the role of autologous stem cell transplantation has been questioned with the advent of novel induction therapies with high complete-remission rates (cited Giralt et al. as reference 83 and Harousseau as reference 84).

Revised text to state that myeloablative allogeneic stem cell transplantation has significant toxic effects, but the possibility of a potent and possibly curative graft-versus-myeloma effect in a minority of patients may offset the high transplant-related mortality (cited Lokhorst et al. as reference 102).

Added text to state that the lower transplant-related mortality from nonmyeloablative approaches has been accompanied by a greater risk of relapse, and it remains debatable whether allogeneic stem cell transplantation should be offered in the first-line setting outside the context of a clinical trial.

Added text to state that clinical trials exploring thalidomide as maintenance therapy have contradictory results.

Revised text to state that maintenance interferon-alpha therapy has been reported to prolong initial remission duration after conventional chemotherapy.

Added text to state that a randomized study compared maintenance interferon with maintenance thalidomide in 103 previously untreated and treated patients who had at least a minimal response to induction chemotherapy with thalidomide, pegylated liposomal doxorubicin, and dexamethasone; with a median follow-up of 30 months, the thalidomide maintenance arm was better (cited Offidani et al. as reference 115 and level of evidence 1iiA).

Added text to state that in a trial of 556 previously untreated patients induced with thalidomide, doxorubicin, dexamethasone, and followed by high-dose melphalan with stem cell support, patients were randomly assigned to alpha interferon or to thalidomide maintenance (cited Lokhorst et al. as reference 24 and level of evidence 1iiA).

Added text about a trial of 269 patients with newly diagnosed myeloma who were given maintenance thalidomide plus prednisolone versus prednisolone alone following both induction therapy and high-dose melphalan with allogeneic stem cell transplantation and showed a benefit in favor of the thalidomide arm after a median follow-up of 3 years (cited Spencer et al. as reference 118 and level of evidence 1iiA).

Added text to state that the optimal use and duration of bisphosphonates for bony involvement in myeloma have not been studied (cited Terpos et al. as reference 126).

Added text about a double-blind, randomized, controlled trial with 504 patients with newly diagnosed multiple myeloma that compared 30 mg of pamidronate to 90 mg of pamidronate and found no difference in skeletal-related events; however, less osteonecrosis was seen in the low-dose group (cited Gimsing et al. as reference 127 and level of evidence 1iDiv).

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about treatment of plasma cell neoplasms (including multiple myeloma). It is intended as a resource to inform and assist clinicians who care for cancer patients. Se ei tarjoa virallisia ohjeita tai suosituksia tehdä terveydenhuollon päätöksiä.

Arvostelijat ja päivitykset

Tämä yhteenveto on tarkistettava säännöllisesti ja päivitetään tarvittaessa PDQ Adult Treatment toimitusneuvosto, joka on toimituksellisesti riippumaton National Cancer Institute (NCI). Yhteenveto kuvastaa riippumaton selvitys kirjallisuuden ja ei edusta poliittisen julkilausuman NCI tai National Institutes of Health (NIH).

Hallituksen jäsenet arvostelu äskettäin julkaissut artikkeleita kuukausittain, onko artikkeli olisi:

keskustellaan kokouksessa, on mainittu tekstin, orreplace tai päivittää olemassa olevia artikkeli, joka on jo mainittu.

Muutokset yhteenvedot ovat kautta yksimielisyyteen prosessi, jossa hallituksen jäsenet arvioivat vahvuus todisteita julkaistuja artikkeleita ja määrittää, miten artikkeli olisi sisällytettävä.

The lead reviewers for Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment are:

Steven D. Gore, MD (Johns Hopkins University)Mark J. Levis, MD, PhD (Johns Hopkins University)Eric J. Seifter, MD (Johns Hopkins University)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Älä ota yksittäisten hallituksen jäsenten kysymyksiä tai kommentteja yhteenvedot. Board members will not respond to individual inquiries.

Tasot Todisteet

Jotkut viittaus sitaattien tässä yhteenvedossa mukana taso-of-näyttöä nimitys. Nämä nimitykset tarkoituksena on auttaa lukijoita arvioimaan vahvuuden käyttöä tukevat todisteet yksittäisten toimien tai lähestymistapoja. PDQ Adult Treatment toimituskunta käyttää virallista näyttöä ranking-järjestelmä kehittämisessä taso-of-näyttöä nimityksiä.

Lupa käyttää tiivistelmää

PDQ on rekisteröity tavaramerkki. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. Kuitenkin kirjailija olisi sallittua kirjoittaa lauseen, kuten "NCI: n PDQ syöpä tietoa yhteenveto siitä rintasyövän ehkäisyä todetaan riskejä ytimekkäästi: [sisältävät ote yhteenveto]."

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional. Pääsee <KK / PP / VVVV>.

kuvat tässä yhteenvedossa käytetään luvalla tekijä (t), taiteilija, ja / tai kustantaja käytettäväksi PDQ yhteenvetoja vain. Lupa käyttää kuvia ulkopuolella yhteydessä PDQ tiedot on saatu omistajan (t) ja ei voi myöntää National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." Näitä luokituksia ei tulisi käyttää perusteena vakuutuksen korvaus määrityksiä. Lisätietoja vakuutusturva on saatavilla Cancer.gov päälle Selviytyminen Cancer: rahoitus-, vakuutus-, ja Legal-sivulla.

Ota yhteyttä

More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Kysymyksiä voi jättää myös Cancer.gov kautta Web-sivuston yhteydenottolomakkeella.

Soita numeroon 1-800-4-Cancer

Lisätietoja Yhdysvaltain asukkaat voivat soittaa National Cancer Instituten (NCI: n) Syöpä tietopalvelu maksuton at 1-800-4-Cancer (1-800-422-6237) maanantaista perjantaihin 08:00-8:00 pm, Itäinen aika. Koulutettu Syöpä informaatikko on valmiina vastaamaan kysymyksiisi.

Keskustele verkossa

NCI: n LiveHelp® chatissa palvelu tarjoaa internetin käyttäjille mahdollisuuden keskustella verkossa informaatikko. The service is available from 8:00 am to 11:00 pm Eastern time, Monday through Friday. Tiedot voivat auttaa Internetin käyttäjiä löytämään tietoa NCI sivustoja ja vastaa kysymyksiin syövästä.

Kirjoita meille

Saat lisätietoja NCI, kirjoita tähän osoitteeseen:

NCI Public Inquiries Office
Suite 3036A
6116 Executive Boulevard, MSC8322
Bethesda, MD 20892-8322

Hae NCI verkkosivustosta

NCI nettisivut tarjoavat pääsyn tietoa syövän, kliinisissä tutkimuksissa ja muihin sivustoihin ja organisaatioita, jotka tarjoavat tukea ja resursseja syöpäpotilaille ja heidän perheilleen. Saat nopea haku, käytä hakukentän oikeassa yläkulmassa jokaisen Web-sivun. Tulokset monenlaisia ​​hakusanojen sisältää listan "Parhaat valinnat," toimituksellisesti valittu Verkkosivut jotka läheisimmin liittyvät hakutermi tuli.

There are also many other places to get materials and information about cancer treatment and services. Sairaalat alueesi saattaa olla tietoa alue- ja paikallisviranomaiset, jotka ovat tietoa talouden, pääsemisestä ja hoitoon, jotka saavat hoitoa kotona, ja käsittelee ongelmia, jotka liittyvät syövän hoitoon.

Etsi Julkaisut

The NCI has booklets and other materials for patients, health professionals, and the public. Nämä julkaisut keskustella syöpien, menetelmiä syövän hoitoon, selviytyä syövän, ja kliinisissä tutkimuksissa. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. Nämä materiaalit voi tilata myös puhelimitse Cancer tietopalvelu maksuton at 1-800-4-Cancer (1-800-422-6237).