Up-front carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRd final results
Murielle Roussel, Valerie Lauwers-Cances, Soraya Wuilleme, Karim Belhadj, Salomon Manier, Laurent Garderet, Martine Escoffre-Barbe, Clara Mariette, Lotfi Benboubker, Denis Caillot, Cécile Sonntag, Cyrille Touzeau, Jehan Dupuis, Philippe Moreau, Xavier Leleu, Thierry Facon, Benjamin Hébraud, Jill Corre, Michel Attal, Murielle Roussel, Valerie Lauwers-Cances, Soraya Wuilleme, Karim Belhadj, Salomon Manier, Laurent Garderet, Martine Escoffre-Barbe, Clara Mariette, Lotfi Benboubker, Denis Caillot, Cécile Sonntag, Cyrille Touzeau, Jehan Dupuis, Philippe Moreau, Xavier Leleu, Thierry Facon, Benjamin Hébraud, Jill Corre, Michel Attal
Abstract
Bortezomib, lenalidomide, and dexamethasone plus transplant is a standard of care for eligible patients with multiple myeloma. Because responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed. In this phase 2 study, patients received eight 28-day cycles of carfilzomib (K) 20/36 mg/m2 (days 1-2, 8-9, 15-16), lenalidomide (R) 25 mg (days 1-21), and dexamethasone (d) 20 mg (days 1-2, 8-9, 15-16, 22-23). All patients proceeded to transplant after 4 cycles and received 1 year of lenalidomide maintenance (10 mg, days 1-21). The primary objective was stringent complete response at the completion of consolidation. Overall, 48 patients were screened and 46 enrolled; 21% had adverse cytogenetics. Among 42 evaluable patients after consolidation, 26 were in stringent complete response (CR; 61.9%), 27 were at least in CR (64.3%): 92.6% had undetectable minimal residual disease according to flow cytometry (≥2.5 × 10-5) and 63.0% according to next-generation sequencing (10-6). Median time to CR was 10.6 months. According to multiparametric flow cytometry and next-generation sequencing, 69.0% and 66.7% of patients, respectively, had undetectable minimal residual disease at some point. With a median follow-up of 60.5 months, 21 patients progressed, and 10 died (7 of multiple myeloma). Median progression-free survival was 56.4 months. There were no KRd-related deaths. Four patients discontinued the program due to toxicities; 56 serious adverse events were reported in 31 patients, including 8 cardiovascular events (2 heart failures, 5 pulmonary embolisms or deep vein thrombosis). Common grade 3/4 adverse events were hematologic (74%) and infectious (22%). In summary, 8 cycles of KRd produce fast and deep responses in transplant-eligible patients with newly diagnosed multiple myeloma. The safety profile is acceptable, but cardiovascular adverse events should be closely monitored. This clinical trial is registered at www.clinicaltrials.gov as #NCT02405364.
© 2021 by The American Society of Hematology.
Source: PubMed