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Superior Outcomes and High-risk Features with Carfilzomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients with Relapsed and Refractory Multiple Myeloma: Results of the Multicenter KMMWP2201 Study

Abstract

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed to investigate this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age, 63 years). The overall response rate was 90% in response-evaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, high-risk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2-3 months prior to start of KRd treatment significantly decreased PFS and OS in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e., delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AE) were observed in 56% of the patients, and non-fatal or fatal AE that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large, real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

References
1.
Berdeja J, Madduri D, Usmani S, Jakubowiak A, Agha M, Cohen A . Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021; 398(10297):314-324. DOI: 10.1016/S0140-6736(21)00933-8. View

2.
Antonioli E, Pilerci S, Attucci I, Buda G, Gozzetti A, Candi V . Carfilzomib, lenalidomide, and dexamethasone in relapsed refractory multiple myeloma: a prospective real-life experience of the Regional Tuscan Myeloma Network. Front Oncol. 2023; 13:1162990. PMC: 10166989. DOI: 10.3389/fonc.2023.1162990. View

3.
Richardson P, San Miguel J, Moreau P, Hajek R, Dimopoulos M, Laubach J . Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting. Blood Cancer J. 2018; 8(11):109. PMC: 6226527. DOI: 10.1038/s41408-018-0141-0. View

4.
Benboubker L, Dimopoulos M, Dispenzieri A, Catalano J, Belch A, Cavo M . Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014; 371(10):906-17. DOI: 10.1056/NEJMoa1402551. View

5.
Kumar S, Jacobus S, Cohen A, Weiss M, Callander N, Singh A . Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3,.... Lancet Oncol. 2020; 21(10):1317-1330. PMC: 7591827. DOI: 10.1016/S1470-2045(20)30452-6. View