This phase 2 trial investigated reinduction with carfilzomib, pomalidomide, and dexamethasone (KPd) and continuous pomalidomide/dexamethasone in patients at first progression during lenalidomide maintenance. The second objective was to evaluate high-dose melphalan with autologous stem cell transplantation (HDM/ASCT) at first progression. Patients were eligible who had progressive disease according to International Myeloma Working Group (IMWG) criteria. Treatment consisted of 8 cycles carfilzomib (20/36 mg/m2), pomalidomide (4 mg) and dexamethasone. Patients without prior transplant received HDM/ASCT. Pomalidomide 4 mg w/o dexamethasone was given until progression. One hundred twelve patients were registered of whom 86 (77%) completed 8 cycles of KPd. Thirty-five (85%) eligible patients received HDM/ASCT. The median time to discontinuation of pomalidomide w/o dexamethasone was 17 months. Best response was 37% ≥ complete response, 75% ≥ very good partial response, 92% ≥ partial response, respectively. At a follow-up of 40 months median PFS was 26 and 32 months for patients who received KPd plus HDM/ASCT and 17 months for patients on KPd (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.37-1.00, P = 0.051). PFS was better after longer duration of prior lenalidomide (HR 3.56, 95% CI 1.42-8.96, P = 0.035). Median overall survival (OS) was 67 months. KPd-emerging grade 3 and 4 adverse events included hematologic (41%), cardiovascular (6%), respiratory (3%), infections (17%), and neuropathy (2%). KPd followed by continuous pomalidomide is an effective and safe triple drug regimen in second-line for patients previously exposed to bortezomib and/or refractory to lenalidomide.

Department of Hematology Amsterdam UMC Vrije Universiteit Amsterdam Cancer Center The Netherlands

Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands

Department of Hematology Haga Hospital The Hague The Netherlands

Department of Hematology La Sapienza Rome Italy

Department of Hematology Ostrava Poruba FNO Czech Republic

Department of Hematology Radboud University Medical Center Nijmegen The Netherlands

Department of Hematology University Medical Center Utrecht Utrecht University The Netherlands

Department of Hematology University of Maastricht Medical Center The Netherlands

Department of Hematology Wilhelminen Hospital Vienna Austria

Department of Molecular Biotechnologies and Health Sciences Hematology Division University of Torino Italy

Division of Hematology Città della Salute e della Scienza Università di Torino Italy

Erasmus MC Cancer Institute Rotterdam The Netherlands

Hematology and Bone Marrow Transplant Unit University of Udine Italy

Hematology Division and Hemato Oncology Department University of Milan Fondazione IRCCS Istituto Nazionale dei Tumori Italy

Hematology Elisabeth Tweesteden Hospital Tilburg The Netherlands

Hematology University Hospital Brno Czech Republic

Hematology University of Torino Italy

Hematology ZNA Stuivenberg Antwerpen Belgium

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università degli Studi Bologna Italy

Hemasphere. 2023 Feb 22;7(3):e856. doi: 10.1097/HS9.0000000000000856. PubMed

Zobrazit více v PubMed

Dimopoulos MA, Moreau P, Terpos E, et al. . Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. HemaSphere. 2021;5:e528. PubMed PMC

Richardson PG, Oriol A, Beksac M, et al. . Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:781–794. PubMed

Palumbo A, Chanan-Khan A, Weisel K, et al. . Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–766. PubMed

Dimopoulos M, Quach H, Mateos MV, et al. . Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396:186–197. PubMed

Dimopoulos MA, Dytfeld D, Grosicki S, et al. . Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma. N Engl J Med. 2018;379:1811–1822. PubMed

Attal M, Richardson PG, Rajkumar SV, et al. . Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019;394:2096–2107. PubMed

Dimopoulos MA, Terpos E, Boccadoro M, et al. . Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22:801–812. PubMed

Cavo M, Gay F, Beksac M, et al. . Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020;7:e456–e468. PubMed

Shah JJ, Stadtmauer EA, Abonour R, et al. . Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015;126:2284–2290. PubMed PMC

Attal M, Lauwers-Cances V, Hulin C, et al. . Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376:1311–1320. PubMed PMC

Stadtmauer EA, Pasquini MC, Blackwell B, et al. . Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol. 2019;37:589–597. PubMed PMC

Durie BG, Harousseau JL, Miguel JS, et al. . International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467–1473. PubMed

Kumar SK, Dimopoulos MA, Kastritis E, et al. . Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study. Leukemia. 2017;31:2443–2448. PubMed

Dimopoulos MA, Oriol A, Nahi H, et al. . Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–1331. PubMed

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;17:27–38. PubMed

San Miguel JF, Weisel KC, Song KW, et al. . Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. Haematologica. 2015;100:1334–1339. PubMed PMC

Mateos MV, Spencer A, Nooka AK, et al. . Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies. Haematologica. 2020;105:468–477. PubMed PMC

Garderet L, Kuhnowski F, Berge B, et al. . Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood. 2018;132:2555–2563. PubMed

Moreau P, Dimopoulos MA, Yong K, et al. . Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design. Future Oncol. 2020;16:4347–4358. PubMed

Dimopoulos M, Weisel K, Moreau P, et al. . Pomalidomide, bortezomib, and dexamethasone for multiple myeloma previously treated with lenalidomide (OPTIMISMM): outcomes by prior treatment at first relapse. Leukemia. 2021;35:1722–1731. PubMed PMC

Dimopoulos MA, Sonneveld P, Siegel D, et al. . Carfilzomib and pomalidomide in patients with relapsed and/or refractory multiple myeloma with baseline risk factors. Ann Oncol. 2015;26:2247–2256. PubMed