P23 EMAGINE/CARTITUDE-6: A RANDOMIZED PHASE 3 STUDY OF DVRD FOLLOWED BY CILTACABTAGENE AUTOLEUCEL VERSUS DVRD FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANT IN TRANSPLANT-ELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
Annemiek Broijl, Jesús F. San Miguel, Kenshi Suzuki, Aparna Krishnan, Niels W.C.J. van de Donk, Gordon Cook, Andrzej Jakubowiak, Deepu Madduri, Salma Afifi, An‐Sofie Stevens, Jordan M. Schecter, William Deraedt, Simone M. Kuppens, Pankaj Mistry, Lida Pacaud, Mario Boccadoro, Francesca Gay, Roberto Mina, Leo Rasche, Philippe Moreau, María‐Victoria Mateos, Hermann Einsele, Pieter Sonneveld
Abstract
Background: Guidelines from the National Comprehensive Cancer Network recommend daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) as induction therapy followed by autologous stem cell transplant (ASCT), consolidation, and maintenance therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). In the phase 1b/2 CARTITUDE-1 study, a single infusion of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR)-T cell therapy with two B-cell maturation antigen (BCMA)-targeting single-domain antibodies, resulted in deep and durable responses with manageable safety in heavily pretreated patients with relapsed/refractory multiple myeloma. The overall response rate (ORR) was 98% (median follow-up of 27.7 months), with 83% of patients achieving stringent complete response (CR); median duration of response was not reached. The aim of this open-label, multicenter, global, phase 3 EMagine/CARTITUDE-6 study (EMN28/68284528MMY3005; NCT05257083) is to evaluate the efficacy of DVRd followed by cilta-cel and lenalidomide versus DVRd followed by ASCT, DVRd, and lenalidomide. Study design and methods: Patients aged ≥18 years with NDMM (per International Myeloma Working Group criteria), measurable disease at screening, and high-dose therapy and ASCT as part of their intended initial treatment plan are eligible. Patients are excluded if they received any prior therapy for multiple myeloma or smoldering myeloma, except a short course of corticosteroids. After providing informed consent, patients are randomized (1:1) into 2 treatment arms, with target recruitment of N=750. In the cilta-cel arm, patients will undergo apheresis before receiving 6 cycles of DVRd induction treatment. After induction, patients will first receive lymphodepletion (intravenous cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days), and then a single infusion of cilta-cel (target dose 0.75×106 CAR+ viable T cells/kg) 5–7 days later. Following cilta-cel infusion, patients will be given lenalidomide post CAR-T therapy for 2 years (or longer, per investigator discretion). The patients in control arm will receive 4 cycles of DVRd induction, then ASCT and 2 cycles of DVRd consolidation, followed by lenalidomide maintenance therapy for 2 years (or longer, per investigator discretion). Dual primary endpoints are progression-free survival (PFS) and minimal residual disease (MRD)-negative CR sustained for ≥12 months. MRD status is assessed by next-generation sequencing at a sensitivity of at least 10-5. The secondary endpoints include ORR, ≥CR rate, overall MRD-negative CR rate, time to subsequent therapy, PFS on next-line therapy, overall survival, adverse events, pharmacokinetic/pharmacodynamic markers, and health-related quality of life. Exploratory correlative biomarker analyses will also be conducted. Enrollment began in September 2022, with expected primary completion in June 2026. This study will explore a cellular therapy approach with cilta-cel versus standard of care ASCT in transplant-eligible patients with NDMM.