Next-generation immunomodulatory drugs in multiple myeloma

REVIEW ARTICLE

Next-generation immunomodulatory drugs in multiple myeloma

Anna Suska 1 , Maciej Rafał Czerniuk 2 , Artur Jurczyszyn 1

1. Katedra Hematologii, Uniwersytet Jagielloński Collegium Medicum, Kraków,
2. Zakład Chirurgii Stomatologicznej Warszawskiego Uniwersytetu Medycznego, Warszawa,

Published: 2019-12-31
DOI: 10.5604/01.3001.0013.6907
GICID: 01.3001.0013.6907
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2019; 73 : 791-802

 

Abstract

Multiple myeloma (MM) is a hematological malignancy that mainly affects elderly patients, with the median age of 69 years at the time of diagnosis. Despite the recent increase in the number of drugs used in the antimyeloma therapy, the disease remains incurable, with remissions and subsequent relapses. Immunomodulatory drugs (IMIDs), known to have multiple mechanisms of actions, including direct anti-MM activity and immune-stimulatory properties, are currently the backbone in multidrug regimens. New generation IMIDs are recommended nowoby ESMO – lenalidomide is included in frontline therapy, while pomalidomide is accepted from the third line. Clinical trials proved lack of apparent cross-resistance between immunomodulatory agents, confirmed their high efficacy and acceptable safety profile in individuals with relapsed multiple myeloma (RRMM) refractory to proteasome inhibitors and lenalidomide, even with adverse cytogenetic abnormalities. Also, triplet pomalidomide-based combinations with bortezomib, carfilzomib, cyclophosphamide, daratumumab or elotuzumab were proved to be effective and safe in this group of patients. The most common adverse events of the new generation IMIDs are the following: hematological toxicity (neutropenia, thrombocytopenia, anemia), fatigue and, while administered with dexamethasone, infections. However, peripheral neuropathy, significantly limiting the use of first generation IMID – thalidomide, is much less frequently observed. Due to the increased risk of venous thromboembolism, thromboprophylaxis should be implemented in the whole course of IMID therapy. Data from real-life settings demonstrate that new generation IMIDs are a cost-effective treatment option in relapsed/ refractory myeloma. Currently, one drug program with the new IMIDs is available in Poland.

References

  • 1. Ailawadhi S., Mikhael J.R., LaPlant B.R., Laumann K.M., KumarS., Roy V., Dingli D., Bergsagel P.L., Buadi F.K., Rajkumar S.V, FonsecaR., Gertz M.A., Kapoor P., Sher T., Hayman S.R. i wsp.: Pomalidomide-dexamethasone in refractory multiple myeloma: long–term follow-up of a multi-cohort phase II clinical trial. Leukemia,2018; 32: 719–728
    Google Scholar
  • 2. American Cancer Society. Survival rates by stage for multiplemyeloma. https://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-survival-rates (21.10.2019)
    Google Scholar
  • 3. Attal M., Lauwers-Cances V., Hulin C., Facon T., Caillot D., EscoffreM., Arnulf B., Macro M., Belhadj K., Garderet L., Roussel M., MathiotC., Avet-Loiseau H., Munshi N.C., Richardson P.G. i wsp.: Autologoustransplantation for multiple myeloma in the era of new drugs:A phase III study of the Intergroupe Francophone Du Myelome (IFM/DFCI 2009 Trial). Blood, 2015; 126: 391–391
    Google Scholar
  • 4. Avet-Loiseau H., Attal M., Moreau P., Charbonnel C., GarbanF., Hulin C., Leyvraz S., Michallet M., Yakoub-Agha I., Garderet L.,Marit G., Michaux L., Voillat L., Renaud M., Grosbois B. i wsp.: Geneticabnormalities and survival in multiple myeloma: the experienceof the Intergroupe Francophone du Myélome. Blood, 2007;109: 3489–3495
    Google Scholar
  • 5. Avet-Loiseau H., Leleu X., Roussel M., Moreau P., Guerin-CharbonnelC., Caillot D., Marit G., Benboubker L., Voillat L., Mathiot C.,Kolb B., Macro M., Campion L., Wetterwald M., Stoppa A.M. i wsp.:Bortezomib plus dexamethasone induction improves outcome ofpatients with t(4;14) myeloma but not outcome of patients withdel(17p). J. Clin. Oncol., 2010; 28: 4630–4634
    Google Scholar
  • 6. Baz R.C., Martin T.G.3rd, Lin H.Y., Zhao X., Shain K.H., Cho H.J.,Wolf J.L., Mahindra A., Chari A., Sullivan D.M., Nardelli L.A., Lau K.,Alsina M., Jagannath S.: Randomized multicenter phase 2 study ofpomalidomide, cyclophosphamide, and dexamethasone in relapsedrefractory myeloma. Blood, 2016; 127: 2561–2568
    Google Scholar
  • 7. Boudreault J.S., Touzeau C., Moreau P.: Triplet combinations in relapsed/refractory myeloma: update on recent phase 3 trials. ExpertRev. Hematol., 2017; 10: 207–215
    Google Scholar
  • 8. Bringhen S., Mina R., Cafro A.M., Liberati A.M., Spada S., BelottiA., Gaidano G., Patriarca F., Troia R., Fanin R., De Paoli L.,Rossi G., Lombardo A., Bertazzoni P., Palumbo A. i wsp.: Once-weeklycarfilzomib, pomalidomide, and low-dose dexamethasonefor relapsed/refractory myeloma: a phase I/II study. Leukemia,2018; 32: 1803–1807
    Google Scholar
  • 9. Celgene Inc.: Produkt monograph: Revlimid®: lenalidomide capsules.Celgene Corporation, Mississauga, Ontario 2019
    Google Scholar
  • 10. Chari A., Suvannasankha A., Fay J.W., Arnulf B., Kaufman J.L.,Ifthikharuddin J.J., Weiss B.M., Krishnan A., Lentzsch S., Comenzo R.,Wang J., Nottage K., Chiu C., Khokhar N.Z., Ahmadi T. i wsp.: Daratumumabplus pomalidomide and dexamethasone in relapsed and/orrefractory multiple myeloma. Blood, 2017; 130: 974–981
    Google Scholar
  • 11. Charlinski G., Grzasko N., Jurczyszyn A., Janczarski M., SzeremetA., Waszczuk-Gajda A., Bernatowicz P., Swiderska A., Guzicka-KazimierczakR., Lech-Maranda E., Szczepaniak A., Wichary R., DmoszynskaA.: The efficacy and safety of pomalidomide in relapsed/refractorymultiple myeloma in a “real-world” study: Polish Myeloma Groupexperience. Eur. J. Haematol., 2018; 101: 354–361
    Google Scholar
  • 12. Chen N., Lau H., Kong L., Kumar G., Zeldis J.B., Knight R., LaskinO.L.: Pharmacokinetics of lenalidomide in subjects with various degreesof renal impairment and in subjects on hemodialysis. J. Clin.Pharmacol., 2007; 47: 1466–1475
    Google Scholar
  • 13. Chen N., Zhou S., Palmisano M.: Clinical pharmacokinetics and pharmacodynamicsof lenalidomide. Clin. Pharmacokinet., 2017; 56: 139–152
    Google Scholar
  • 14. Dimopoulos M.A., Dytfeld D., Grosicki S., Moreau P., Takezako N.,Hori M., Leleu X., LeBlanc R., Suzuki K., Raab M.S., Richardson P.G.,Popa McKiver M., Jou Y.M., Shelat S.G., Robbins M. i wsp.: Elotuzumabplus pomalidomide and dexamethasone for multiple myeloma.N. Engl. J. Med., 2018; 379: 1811–1822
    Google Scholar
  • 15. Dimopoulos M.A., Leleu X., Palumbo A., Moreau P., Delforge M.,Cavo M., Ludwig H., Morgan G.J., Davies F.E., Sonneveld P., Schey S.A.,Zweegman S., Hansson M., Weisel K., Mateos M.V. i wsp.: Expert panelconsensus statement on the optimal use of pomalidomide in relapsedand refractory multiple myeloma. Leukemia, 2014; 28: 1573–1585
    Google Scholar
  • 16. Dimopoulos M.A., Palumbo A., Attal M., Beksaç M., DaviesF.E., Delforge M., Einsele H., Hajek R., Harousseau J.L., da CostaF.L., Ludwig H., Mellqvist U.H., Morgan G.J., San-Miguel J.F., ZweegmanS. i wsp.: Optimizing the use of lenalidomide in relapsedor refractory multiple myeloma: consensus statement. Leukemia,2011; 25: 749–760
    Google Scholar
  • 17. Dimopoulos M.A., Palumbo A., Corradini P., Cavo M., DelforgeM., Di Raimondo F., Weisel K.C., Oriol A., Hansson M., Vacca A., BlanchardM.J., Goldschmidt H., Doyen C., Kaiser M., Petrini M. i wsp.:Safety and efficacy of pomalidomide plus low-dose dexamethasonein STRATUS (MM-010): a phase 3b study in refractory multiple myeloma.Blood, 2016; 128: 497–503
    Google Scholar
  • 18. Dimopoulos M.A., Weisel K., Song K.W., Delforge M., Karlin L.,Goldschmidt H., Moreau P., Banos A., Oriol A., Garderet L., Cavo M.,Ivanova V., Alegre A., Martinez-Lopez J., Chen C.I. i wsp.: Final analysis,cytogenetics, long-term treatment, and long-term survival inMM-003, a phase 3 study comparing pomalidomide + low-dose dexamethasone(POM + LoDEX) vs high-dose dexamethasone (HiDEX) inrelapsed/refractory multiple myeloma (RRMM). Blood, 2013; 122: 408
    Google Scholar
  • 19. Dimopoulos M.A., Weisel K.C., Song K.W., Delforge M., Karlin L.,Goldschmidt H., Moreau P., Banos A., Oriol A., Garderet L., Cavo M.,Ivanova V., Alegre A., Martinez-Lopez J., Chen C. i wsp.: Cytogeneticsand long-term survival of patients with refractory or relapsed andrefractory multiple myeloma treated with pomalidomide and low–dose dexamethasone. Haematologica, 2015; 100: 1327–1333
    Google Scholar
  • 20. Dimopoulos M., Weisel K., van de Donk N.W., Ramasamy K.,Gamberi B., Streetly M., Offidani M., Bridoux F., de la Rubia J., MateosM.V., Ardizzoia A., Kueenburg E., Collins S., Di Micco A., RosettaniB. i wsp.: Pomalidomide plus low-dose dexamethasone in patientswith relapsed/refractory multiple myeloma and renal impairment:results from a phase II trial. J. Clin. Oncol., 2018; 36: 2035–2043
    Google Scholar
  • 21. Durie B.G., Hoering A., Abidi M.H., Rajkumar S.V., Epstein J.,Kahanic S.P., Thakuri M., Reu F., Reynolds C.M., Sexton R., OrlowskiR.Z., Barlogie B., Dispenzieri A.: Bortezomib with lenalidomide anddexamethasone versus lenalidomide and dexamethasone alone inpatients with newly diagnosed myeloma without intent for immediateautologous stem-cell transplant (SWOG S0777): a randomised,open-label, phase 3 trial. Lancet, 2017; 389: 519–527
    Google Scholar
  • 22. Franssen L.E., Mutis T., Lokhorst H.M., van de Donk N.W.: Immunotherapyin myeloma: how far have we come ? Ther. Adv. Hematol.,2019; 10: 2040620718822660
    Google Scholar
  • 23. Gandhi A.K., Kang J., Havens C.G., Conklin T., Ning Y., Wu L., ItoT., Ando H., Waldman M.F., Thakurta A., Klippel A., Handa H., DanielT.O., Schafer P.H., Chopra R.: Immunomodulatory agents lenalidomideand pomalidomide co-stimulate T cells by inducing degradationof T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitinligase complex CRL4(CRBN.). Br. J. Haematol., 2014; 164: 811–821
    Google Scholar
  • 24. Garderet L., Kuhnowski F., Berge B., Roussel M., Escoffre-BarbeM., Lafon I., Facon T., Leleu X., Karlin L., Perrot A., Moreau P., MaritG., Stoppa A.M., Royer B., Chaleteix C. i wsp.: Pomalidomide, cyclophosphamide,and dexamethasone for relapsed multiple myeloma.Blood, 2018; 132: 2555–2563
    Google Scholar
  • 25. Giannopoulos K., Jamroziak K., Usnarska-Zubkiewicz L., DytfeldD., Jurczyszyn A., Walewski J., Lech-Marańda E., Walter-Croneck A.,Pieńkowska-Grela B., Wróbel T., Charliński G., Jędrzejczak W.W., MałkowskiB., Druzd-Sitek A., Robak T. i wsp.: Zalecenia Polskiej GrupySzpiczakowej dotyczące rozpoznawania i leczenia szpiczaka plazmocytowegooraz innych dyskrazji plazmocytowych na rok 2018/2019.Acta Haematol. Pol., 2018; 49: 157–206
    Google Scholar
  • 26. Gooding S., Lau I.J., Sheikh M., Roberts P., Wong J., Dickens E.,Elvidge J., Lee D., Ramasamy K.: Double refractory myeloma: Analysisof clinical outcomes and medical-resource utilisation in a singlecentre. Blood, 2013; 122: 1727
    Google Scholar
  • 27. Gueneau P., Chretien M.L., Cransac-Miet A., Aho L.S., Lafon I.,Favennec C., Guy J., Caillot D., Boulin M.: Efficacy, safety, and cost ofpomalidomide in relapsed and refractory multiple myeloma. Eur. J.Haematol., 2018; 100: 518–525
    Google Scholar
  • 28. Jurczyszyn A., Legieć W., Helbig G., Hus M., Kyrcz-Krzemień S.,Skotnicki A.B.: New drugs in multiple myeloma – role of carfilzomiband pomalidomide. Contemp. Oncol., 2014; 18: 17–21
    Google Scholar
  • 29. Krishnan A., Kapoor P., Palmer J.M., Tsai N.C., Kumar S., LonialS., Htut M., Karanes C., Nathwani N., Rosenzweig M., Sahebi F., SomloG., Duarte L., Sanchez J.F., Auclair D. i wsp.: Phase I/II trial of the oralregimen ixazomib, pomalidomide, and dexamethasone in relapsed/refractory multiple myeloma. Leukemia, 2017 (w druku)
    Google Scholar
  • 30. Kumar S.K., Lee J.H., Lahuerta J.J., Morgan G., Richardson P.G.,Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X.,Hulin C., Klein S.K., Sonneveld P., Siegel D. i wsp.: Risk of progressionand survival in multiple myeloma relapsing after therapy with IMiDsand bortezomib: a multicenter international myeloma working groupstudy. Leukemia, 2012; 26: 149–157
    Google Scholar
  • 31. Kyle R.A., Rajkumar S.V.: Multiple myeloma. N. Engl. J. Med.,2004; 351: 1860–1873
    Google Scholar
  • 32. Leleu X., Attal M., Arnulf B., Moreau P., Traulle C., Marit G., MathiotC., Petillon M.O., Macro M., Roussel M., Pegourie B., Kolb B.,Stoppa A.M., Hennache B., Bréchignac S. i wsp.: Pomalidomide pluslow-dose dexamethasone is active and well tolerated in bortezomiband lenalidomide refractory multiple myeloma: Intergroupe Francophonedu Myélome 2009-02. Blood, 2013; 121: 1968–1975
    Google Scholar
  • 33. Leleu X., Karlin L., Macro M., Hulin C., Garderet L., Roussel M.,Arnulf B., Pegourie B., Kolb B., Stoppa A.M., Brechiniac S., MaritG., Thielemans B., Onraed B., Mathiot C. i wsp.: Pomalidomide pluslow-dose dexamethasone in multiple myeloma with deletion 17pand/or translocation (4;14): IFM 2010-02 trial results. Blood, 2015;125: 1411–1417
    Google Scholar
  • 34. Lopez-Girona A., Mendy D., Ito T., Miller K., Gandhi A.K., KangJ., Karasawa S., Carmel G., Jackson P., Abbasian M., Mahmoudi A.,Cathers B., Rychak E., Gaidarova S., Chen R. i wsp.: Cereblon isa direct protein target for immunomodulatory and antiproliferativeactivities of lenalidomide and pomalidomide. Leukemia,2012; 26: 2326–2335
    Google Scholar
  • 35. Ludwig H., Delforge M., Facon T., Einsele H., Gay F., Moreau P.,Avet-Loiseau H., Boccadoro M., Hajek R., Mohty M., Cavo M., DimopoulosM.A., San-Miguel J.F., Terpos E., Zweegman S. i wsp.: Preventionand management of adverse events of novel agents in multiplemyeloma: A consensus of the European Myeloma Network. Leukemia,2018; 32: 1542–1560
    Google Scholar
  • 36. McCarthy P.L., Holstein S.A., Petrucci M.T., Richardson P.G.,Hulin C., Tosi P., Bringhen S., Musto P., Anderson K.C., Caillot D.,Gay F., Moreau P., Marit G., Jung S.H., Yu Z. i wsp.: Lenalidomidemaintenance after autologous stem-cell transplantation in newlydiagnosed multiple myeloma: A meta–analysis. J. Clin. Oncol.,2017; 35: 3279–3289
    Google Scholar
  • 37. Menon S.P., Rajkumar S.V., Lacy M., Falco P., Palumbo A.: Thromboembolicevents with lenalidomide-based therapy for multiplemyeloma. Cancer, 2008; 112: 1522–1528
    Google Scholar
  • 38. Miguel J.S., Weisel K., Moreau P., Lacy M., Song K., Delforge M.,Karlin L., Goldschmidt H., Banos A., Oriol A., Alegre A., Chen C., CavoM., Garderet L., Ivanova V.: Pomalidomide plus low-dose dexamethasoneversus high-dose dexamethasone alone for patients withrelapsed and refractory multiple myeloma (MM-003): a randomised,open-label, phase 3 trial. Lancet Oncol., 2013; 14: 1055–1066
    Google Scholar
  • 39. Moreau P., Dimopoulos M.A., Richardson P.G., Siegel D.S., CavoM., Corradini P., Weisel K., Delforge M., O’Gorman P., Song K., ChenC., Bahlis N., Oriol A., Hansson M., Kaiser M. i wsp.: Adverse eventmanagement in patients with relapsed and refractory multiple myelomataking pomalidomide plus low-dose dexamethasone: A pooledanalysis. Eur. J. Haematol., 2017; 99: 199–206
    Google Scholar
  • 40. Moreau P., San Miguel J., Sonneveld P., Mateos M.V., Zamagni E.,Avet-Loiseau H., Hajek R., Dimopoulos M.A., Ludwig H., Einsele H.,Zweegman S., Facon T., Cavo M., Terpos E., Goldschmidt H.: Multiplemyeloma: ESMO Clinical Practice Guidelines for diagnosis, treatmentand follow-up. Ann. Oncol., 2017; 28: iv52–iv61
    Google Scholar
  • 41. Morgan G., Palumbo A., Dhanasiri S., Lee D., Weisel K., Facon T.,Delforge M., Oriol A., Zaki M., Yu X., Sternas L., Jacques C., AkehurstR., Offner F., Dimopoulos M.A.: Overall survival of relapsed and refractorymultiple myeloma patients after adjusting for crossover inthe MM-003 trial for pomalidomide plus low-dose dexamethasone.Br. J. Haematol., 2015; 168: 820–823
    Google Scholar
  • 42. Musallam K.M., Dahdaleh F.S., Shamseddine A.I., Taher A.T.:Incidence and prophylaxis of venous thromboembolic events inmultiple myeloma patients receiving immunomodulatory therapy.Thromb. Res., 2009; 123: 679–686
    Google Scholar
  • 43. Paludo J., Mikhael J.R., LaPlant B.R., Halvorson A.E., KumarS., Gertz M.A., Hayman S.R., Buadi F.K., Dispenzieri A., Lust J.A.,Kapoor P., Leung N., Russell S.J., Dingli D., Go R.S. i wsp.: Pomalidomide,bortezomib, and dexamethasone for patients with relapsedlenalidomide-refractory multiple myeloma. Blood, 2017;130: 1198–1204
    Google Scholar
  • 44. Palumbo A., Bringhen S., Kumar S.K., Lupparelli G., Usmani S.,Waage A., Larocca A., van der Holt B., Musto P., Offidani M., PetrucciM.T., Evangelista A., Zweegman S., Nooka A.K., Spencer A. i wsp.:Second primary malignancies with lenalidomide therapy for newlydiagnosed myeloma: a meta-analysis of individual patient data.Lancet Oncol., 2014; 15: 333–342
    Google Scholar
  • 45. Pelligra C.G., Parikh K., Guo S., Chandler C., Mouro J., AbouzaidS., Ailawadhi S.: Cost-effectiveness of pomalidomide, carfilzomib,and daratumumab for the treatment of patients with heavily pretreatedrelapsed-refractory multiple myeloma in the United States.Clin. Ther., 2017; 39: 1986–2005
    Google Scholar
  • 46. Rajkumar S.V., Dimopoulos M.A., Palumbo A., Blade J., MerliniG., Mateos M.V., Kumar S., Hillengass J., Kastritis E., Richardson P.,Landgren O., Paiva B., Dispenzieri A., Weiss B., Leleu X. i wsp.: InternationalMyeloma Working Group updated criteria for the diagnosisof multiple myeloma. Lancet Oncol., 2014; 15: e538–e548
    Google Scholar
  • 47. Reece D., Song K.W., Fu T., Roland B., Chang H., Horsman D.E.,Mansoor A., Chen C., Masih-Khan E., Trieu Y., Bruyere H., StewartD.A., Bahlis N.J.: Influence of cytogenetics in patients with relapsedor refractory multiple myeloma treated with lenalidomideplus dexamethasone: adverse effect of deletion 17p13. Blood,2009; 114: 522–525
    Google Scholar
  • 48. Richardson P.G., Hofmeister C.C., Raje N.S., Siegel D.S., LonialS., Laubach J., Efebera Y.A., Vesole D.H., Nooka A.K., Rosenblatt J.,Doss D., Zaki M.H., Bensmaine A., Herring J., Li Y.: Pomalidomide,bortezomib and low–dose dexamethasone in lenalidomide-refractoryand proteasome inhibitor-exposed myeloma. Leukemia, 2017;31: 2695–2701
    Google Scholar
  • 49. Richardson P.G., Oriol A., Becsac M., Leberati A.M., Galli M., SchjesvoldF., Lindsay J., Weisel K., White D., Facon T., San Miguel J., SunamiK., O’Gorman P., Sonneveld P., Robak P. et al.: Pomalidomide, bortezomib,and dexamethasone for patient with relapsed or refractory multiplemyeloma proviously treated with lenolidomide (OPTIMISMM): arandomised, open-label, phase 3 trial. Lancet Oncol., 2019; 20: 781-794
    Google Scholar
  • 50. Richardson P.G., Siegel D.S., Vij R., Hofmeister C.C., Baz R., JagannathS., Chen C., Lonial S., Jakubowiak A., Bahlis N., Song K., Belch A., RajeN., Shustik C., Lentzsch S. i wsp.: Pomalidomide alone or in combinationwith low-dose dexamethasone in relapsed and refractory multiplemyeloma: a randomized phase 2 study. Blood, 2014; 123: 1826–1832
    Google Scholar
  • 51. Roig M., Ibañez A., García I., Vera J.A., Aguilar C., del Campo R.,Gonzalez N., Martínez R., Palomera L., Picon I., Rodríguez J.N., MiguelS.A., de la Rubia J.: Activity and safety of lenalidomide and dexamethasonein multiple myeloma patients with advanced renal failure:A Spanish multicenter retrospective study. Blood, 2009; 114: 1886
    Google Scholar
  • 52. Roy A., Kish J.K., Bloudek L., Siegel D.S., Jagannath S., Globe D.,Kuriakose E.T., Migliaccio-Walle K.: Estimating the costs of therapy inpatients with relapsed and/or refractory multiple myeloma: a modelframework. Am. Health Drug Benefits, 2015; 8: 204–215
    Google Scholar
  • 53. San-Miguel J.F., Mateos M.V.: Can multiple myeloma becomea curable disease? Haematologica, 2011; 96: 1246–1248
    Google Scholar
  • 54. Shah J.J., Stadtmauer E.A., Abonour R., Cohen A.D., BensingerW.I., Gasparetto C., Kaufman J.L., Lentzsch S., Vogl D.T., Gomes C.L.,Pascucci N., Smith D.D., Orlowski R.Z., Durie B.G.: Carfilzomib, pomalidomide,and dexamethasone for relapsed or refractory myeloma.Blood, 2015; 126: 2284–2290
    Google Scholar
  • 55. Tarant J.L., Ashcroft J., Feyler S., Owen R.G., Parrish C., Cook G.:Treatment patterns, survival in multiple myeloma patients sequentiallyexposed to thalidomide, bortezomib, lenalidomide in a UKsingle centre. Blood, 2013; 122: 5380
    Google Scholar
  • 56. Trudel S., Tessoulin B., Jullien M., Blin N., Gastinne T., MahéB., Dubruille V., Bonnet A., Lok A., Chevallier P., Peterlin P., GarnierA., Guillaume T., Le Bourgeois A., Le Gouill S. i wsp.: Pomalidomide,cyclophosphamide, and dexamethasone for relapsed/refractorymultiple myeloma patients in a real-life setting: a single-center retrospectivestudy. Ann. Hematol., 2019; 98: 1441–1447
    Google Scholar

Full text

Skip to content