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How to sequence BCMA-directed therapies in early relapsed/ refractory multiple myeloma
At the ESH 7th Translational Research Conference:
Multiple Myeloma
with Martin Kaiser, Mohamad Mohty, and Rakesh Popat
Saturday, October 5, 2024 | 09:10-10:10 CEST
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Multiple myeloma (MM) is the second most frequent hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias which begins with monoclonal gammopathy of unknown significance to overt plasma cell leukemia and extramedullary myeloma. Transplant eligibility continues to define initial MM treatment.1 As MM predominantly affects elderly patients, >50% of patients are not candidates for autologous stem cell transplantation, which has typically been offered to patients aged <65 years.1 As outcomes in transplant-ineligible patients are worse than in transplant-eligible patients, and there remains an unmet need to explore better treatment options for this population.
Previous studies (VISTA, UPFRONT, and ENDEAVOR) have demonstrated improvements in progression-free survival (PFS) and overall survival (OS).2,3 Based on these results Professor Thierry Facon from the Lille University Hospital, Lille, France, and colleagues, initiated a randomized, open-label, multicenter, phase III study (CLARION; NCT01818752) to compare Carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible NDMM patients. The primary objective of the study was to compare PFS between the two regimens.4
The study found that there was no statistically significant difference in PFS between the treatment regimens of KMP and VMP in transplant-ineligible NDMM patients. Increased toxicity in the carfilzomib group of CLARION may explain clinical outcomes, and melphalan may not be an ideal drug to combine with carfilzomib in this setting. The study suggested that alternative carfilzomib based regimens merit further evaluation in NDMM patients.
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