Upfront Carfilzomib, Lenalidomide, Dexamethasone with Transplant in Multiple Myeloma Patients, the IFM KRd final results.

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Bortezomib, lenalidomide, dexamethasone plus transplant is a standard of care for eligible Multiple Myeloma patients. As responses can deepen with time, regimens with longer and more potent induction/consolidation phases are needed. In this phase II study, patients received eight 28-day cycles of carfilzomib (K) 20/36mg/m2 (D1-2,8-9,15-16), lenalidomide (R) 25 mg (D1-21), and dexamethasone (d) 20 mg (D1-2,8-9,15-16,22-23). All patients proceeded to transplant after 4 cycles and received 1-year lenalidomide maintenance (10 mg, D1-21). The primary objective was stringent complete response (sCR) 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 sCR (61.9%), 27 in ≥CR (64.3%): 92.6% had undetectable Minimal Residual Disease by flow cytometry (≥2.5 x10-5) and 63.0% by next generation sequencing (10-6). Median time to CR was 10.6 months. By MFC and NGS, 69.0% and 66.7% patients, respectively had undetectable MRD at some point. With a median follow-up of 60.5 months, 21 patients progressed and 10 died (7 from MM). Median PFS was 56.4 months. There was no KRd related death. Four patients discontinued the program due to toxicities; 56 serious AEs were reported in 31 patients including 8 cardiovascular events (2 heart failures, 5 pulmonary embolisms or deep vein thrombosis). Common grade 3/4 AEs were hematological (74%) and infectious (22%). In conclusion, 8 cycles of KRd produce fast and deep responses in transplant eligible NDMM patients. Safety profile is acceptable but cardiovascular AEs should be closely monitored.

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Authors: Murielle Roussel, Valerie Lauwers-Cances, Soraya Wuilleme, Karim Belhadj, Salomon Manier, Laurent Garderet, Martine Escoffre-Barbe, Slara Mariette, Lotfi Benboubker, Denis Caillot, Cécile Sonntag, Cyrille Touzeau, Jehan Dupuis, Philippe Moreau, Xavier Leleu, Thierry Facon, Benjamin Hébraud, Jill Corre, Michel Attal