Depth of response to isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: Interim analysis of the GMMG-CONCEPT trial.
Katja Weisel, Anne Marie Asemissen, Britta Besemer, Mathias Haenel, Igor Wolfgang Blau, Martin Göerner, Yon‐Dschun Ko, Jan Dürig, Peter Staib, Christoph Mann, Raphael Lutz, Markus Munder, Ullrich Graeven, Rudolph Peceny, Hans Salwender, Manola Zago, Axel Benner, Diana Tichy, Carsten Bokemeyer, Hartmut Goldschmidt
Abstract
8508 Background: High-risk (HR) multiple myeloma (MM) still has a significant impaired prognostic outcome. Addition of CD38 monoclonal antibodies to standard-of-care regimens significantly improved response rates and depth of response in newly diagnosed (ND) and relapsed/refractory MM patients (pts). Here, we report the prespecified end of induction interim analysis (IA) of the investigator-initiated GMMG-CONCEPT trial (NCT03104842), evaluating the quadruplet regimen isatuximab plus carfilzomib, lenalidomide and dexamethasone (Isa-KRd) in HR NDMM pts. Methods: 153 pts with HR NDMM are planned to be included into the trial. HR MM is defined by the presence of del17p or t(4;14) or t(14;16) or > 3 copies 1q21 and ISS 2 or 3 stage disease. Pts receive 6 cycles of Isa-KRd induction, 4 cycles of Isa-KRd consolidation and Isa-KR maintenance. Transplant eligible pts (arm A) undergo high-dose therapy. Transplant ineligible pts (arm B) receive 2 additional cycles of Isa-KRd induction. The primary endpoint is MRD negativity measured by next-generation flow after consolidation. This IA reports on overall response rates (ORR) after induction. Additional MRD analysis will be presented. Results: 50 pts (46 arm A, 4 arm B) were included in the IA population for ORR. HR MM was defined by del17p in 52%, t(4;14) in 38%, t(14;16) in 12% and > 3 copies 1q21 in 42%. 39/46 pts in arm A and 4/4 pts in arm B completed induction treatment. ORR was 100%, with 5 pts (10.0%) showing partial response (PR), 22 (44.0%; including 4 in arm B) very good partial response (VGPR) and 23 (46.0 %) complete response (CR). Median stem cell yield was 6.6 × 10 6 CD34+ cells/kg. Grade 3/4 treatment-emergent adverse events (≥ 10%) with Isa-KRd included neutropenia (34.0%), leukopenia (26.0%) and thrombocytopenia (14.0%). Main non-hematologic toxicities grade 3/4 were hypertension (12.0%) and infection (8.0%). Conclusions: To the best of our knowledge, we report for the first time on a trial investigating solely HR NDMM and Isa-KRd quadruplet treatment. Isa-KRd induction induces deep responses in HR MM pts. The overall safety profile of Isa-KRd is expected and consistent with previous reports. The study is ongoing, with pts continuing to be included. Clinical trial information: 03104842 .