Carfilzomib, lenalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience
- Authors: Zherebtsova V.A.1, Vorobyev V.I.1, Gemdzhian E.G.2, Ulyanova M.A.1, Chernikov M.V.3, Ivanova V.L.1, Vinogradova O.Y.1, Ptushkin V.V.1
-
Affiliations:
- Botkin City Clinical Hospital
- National Research Center for Hematology
- Research Institute of Health Organization and Medical Management
- Issue: Vol 93, No 7 (2021)
- Pages: 785-792
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/76318
- DOI: https://doi.org/10.26442/00403660.2021.07.200956
- ID: 76318
Cite item
Full Text
Abstract
Background. Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial.
Aim. Analysis of efficacy and safety of KRd in routine clinical practice.
Materials and methods. The prospective analysis included patients with MM who received at least one line of previous therapy. The inclusion criteria were relapse/progression; refractoriness; lack of very good partial response (VGPR) and more after the first line of therapy. Since February 2016, we used KRd like in ASPIRE trial, since October 2019, carfilzomib has been used at a dose of 56 mg/m2 on days 1, 8 and 15. Autologous hematopoietic stem cell transplantation (autoHSCT), consolidation (KRd) and maintenance therapy (Rd) were regarded as one line of therapy.
Results and discussion. We evaluated 77 patients with median age at the time of diagnosis is 55 (30–72) years. For 56% (n=43) of patients KRd was applied as the second line (group 1), for 44% (n=34) – as the third and more (group 2). In 23/43 patients from group 1, an early change in therapy was made due to insufficient effectiveness (after 2–4 courses of VCD or PAD). KRd served as a "bridge" to autoHSCT in 25 (32%) patients (21 of 25 in group 1). Another 7 patients underwent collection of autoHSC (all from group 1).
The overall response rate (ORR) was 80.5%, with 33.8% complete response (CR) and 26% VGPR. ORR in group 1 was 98% versus 65.6% in group 2; 24-month overall survival (OS) was 70%, progression free survival (PFS) – 49.8%. In group 1, 24-month OS was 85.6% versus 50.0% in group 2, 24-month PFS was 67.8% versus 25.5% (p=0.01).
Conclusion. Our analysis confirmed the high efficiency of KRd in the treatment of RRMM in real-life practice. Early correction of therapy with insufficient effectiveness of the first line made it possible to implement the strategy of high-dose consolidation and autoHSCT in a larger percentage of patients with MM.
Full Text
##article.viewOnOriginalSite##About the authors
Vera A. Zherebtsova
Botkin City Clinical Hospital
Author for correspondence.
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-3052-269X
канд. мед. наук, врач-гематолог отд-ния трансплантации костного мозга и гемопоэтических стволовых клеток №56
Russian Federation, MoscowVladimir I. Vorobyev
Botkin City Clinical Hospital
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-2692-8961
канд. мед. наук, врач-гематолог, зав. отд-нием трансплантации костного мозга и гемопоэтических стволовых клеток №56
Russian Federation, MoscowEduard G. Gemdzhian
National Research Center for Hematology
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-8357-977X
ст. науч. сотр. лаб. биостатистики
Russian Federation, MoscowMargarita A. Ulyanova
Botkin City Clinical Hospital
Email: vera_ger@mail.ru
ORCID iD: 0000-0003-4977-1482
врач-гематолог отд-ния трансплантации костного мозга и гемопоэтических стволовых клеток №56
Russian Federation, MoscowMikhail V. Chernikov
Research Institute of Health Organization and Medical Management
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-7869-209X
программист организационно-методического отд. по гематологии
Russian Federation, MoscowValentina L. Ivanova
Botkin City Clinical Hospital
Email: vera_ger@mail.ru
ORCID iD: 0000-0001-9272-1742
врач-гематолог, зав. клинико-диагностическим отд-нием
Russian Federation, MoscowOlga Yu. Vinogradova
Botkin City Clinical Hospital
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-3669-0141
д-р мед. наук, врач-гематолог, зав.
Russian Federation, MoscowVadim V. Ptushkin
Botkin City Clinical Hospital
Email: vera_ger@mail.ru
ORCID iD: 0000-0002-9368-6050
д-р мед. наук, врач-гематолог, зам. глав. врача по медицинской части (гематологии)
Russian Federation, MoscowReferences
- Злокачественные новообразования в России в 2017 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018 [Malignant neoplasms in Russia in 2017 (morbidity and mortality). Ed. by AD Kaprin, VV Starinsky, GV Petrova. Moscow: Herzen Moscow State Medical Research Institute – branch of the Federal State Budgetary Institution "NMIC of Radiology" of the Ministry of Health of Russia, 2018 (in Russian)].
- Лучинин А.С., Семочкин С.В., Минаева Н.В., и др. Эпидемиология множественной миеломы по данным анализа популяционного регистра Кировской области. Онкогематология. 2017;12(3):50-6 [Luchinin AS, Semochkin SV, Minaeva NV, et al. Epidemiology of multiple myeloma according to the Kirov Region population registers. Oncohematology. 2017;12(3):50-6 (in Russian)]. doi: 10.17650/1818-8346-2017-12-3-50-56
- Скворцова Н.В., Поспелова Т.И., Ковынев И.Б., и др, Эпидемиология множественной миеломы в Новосибирске (Сибирский федеральный округ). Клиническая онкогематология. 2019;12(1):86-94 [Skvortsova NV, Pospelova TI, Kovynev IB, et al. Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District). Clinical Oncohematology. 2019;12(1):86-94 (in Russian)]. doi: 10.21320/2500-2139-2019-12-1-86-94
- Виноградова О.Ю., Птушкин В.В., Черников М.В., и др. Эпидемиология множественной миеломы в городе Москва. Терапевтический архив. 2019;91(7):83-92 [Vinogradova OYu, Ptushkin VV, Chernikov MV, et al. Epidemiology of multiple myeloma in city Moscow. Terapevticheskii Arkhiv (Ter. Arkh). 2019;91(7):83-92 (in Russian)]. doi: 10.26442/00403660.2019.07.000305
- Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl. 4):iv52-iv61. doi: 10.1093/annonc/mdx096
- Zou Ya, Lin M, Sheng Zh, Niu S. Bortezomib and lenalidomide as front-line therapy for multiple myeloma. Leuk Lymphoma. 2014;55(9):2024-31. doi: 10.3109/10428194.2013.847935
- Facon T, Dimopoulos MA, Dispenzieri A, et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood. 2018;131(3):301-10. doi: 10.1182/blood-2017-07-795047
- Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-28. doi: 10.1056/NEJMoa1714678
- Sivaraj D, Bacon W, Long GD, et al. High-dose BCNU/Melphalan conditioning regimen before autologous stem cell transplantation in newly diagnosed multiple myeloma. Bone Marrow Transplant. 2018;53(1):34-8. doi: 10.1038/bmt.2017.208
- Dhakal B, Szabo A, Chhabra S, et al. Autologous transplantation for newly diagnosed multiple myeloma in the era of novel agent induction a systematic review and meta-analysis. JAMA Oncol. 2018;4(3):343-50. doi: 10.1001/jamaoncol.2017.4600
- Su B, Zhu X, Jiang Y, et al. A meta-analysis of autologous transplantation for newly diagnosed multiple myeloma in the era of novel agents. Leuk Lymphoma. 2018;60. doi: 10.1080/10428194.2018.1543874
- Dingli D, Ailawadhi S, Bergsagel PL, et al. Therapy for relapsed multiple myeloma: guidelines from the Mayo stratification for myeloma and risk-adapted therapy. Mayo Clin Proc. 2017; 92:578-98. doi: 10.1016/j.mayocp.2017.01.003
- Harousseau JL, Attal M. How I treat first relapse of myeloma. Blood. 2017;130:963-73. doi: 10.1182/blood-2017-03-726703
- Sonneveld P, Broijl A. Treatment of relapsed and refractory multiple myeloma. Haematologica. 2016;101:396-406. doi: 10.3324/haematol.2015.129189
- Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79:867-74. doi: 10.4065/79.7.867
- Durie BG, Moreau P, Sonneveld P, et al. Regional differences in the treatment approaches for relapsed multiple myeloma: an IMF study. J Clin Oncol. 2012;30:8095. doi: 10.1200/JCO.2012.30.15_SUPPL.8095
- Siegel DS, Dimopoulos MA, Ludwig H, et al. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36:728-34. doi: 10.1200/JCO.2017.76.5032
- Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. New Engl J Med. 2015;372:142-52. doi: 10.1056/NEJMoa1411321
- Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467-73. doi: 10.1038/sj.leu.2404284
- Cancer Therapy Evaluation Program CTCAE, version 4.03. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_30. Accessed: 14.06.2010.
- Dimopoulos MA, Wang M, Maisnar V, et al. Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study. J Hematology Oncology. 2018;11:49. doi: 10.1186/s13045-018-0583-7
- Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27-38. doi: 10.1016/S1470-2045(15)00464-7
- Jasielec JK, Kubicki T, Raje N, et al. Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma, Blood. 2020;136:2513-23. doi: 10.1182/blood.2020007522
- Jakubowiak AJ, Dytfeld D, Griffith Kent A, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood. 2012;120. doi: 10.1182/blood-2012-04-422683
- Facon T, Lee JH, Moreau P, et al. Randomized phase 3 study of carfilzomib with melphalan-prednisone for transplant-ineligible, NDMM patients. Blood. 2019;133(18):1953-63. doi: 10.1182/blood-2018-09-874396
- Kumar S, Jacobus SJ, Cohen AD, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) for initial therapy of newly diagnosed multiple myeloma (NDMM): Results of ENDURANCE (E1A11) phase III trial [abstract]. J Clin Oncol. 2020;38(18). Abstract LBA3.
- Gay F, Cerrato C, Petrucci MT. et al. Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: results from the FORTE trial. J Clin Oncol. 2019;37. doi: 10.1200/JCO.2019.37.15_suppl.8002
- Takamatsu H, Yoroidaka T, Fujisawa M, et al. Comparison of minimal residual disease detection in multiple myeloma by SRL 8-color single-tube and EuroFlow 8-color 2-tube multiparameter flow cytometry. Int J Hematol. 2019;109(4):377-81. doi: 10.1007/s12185-019-02615-z
Supplementary files
![](/img/style/loading.gif)