Deepening responses and MRD-conversion in a phase II fixed-duration consolidation trial of elranatamab post-idecabtagene vicleucel CAR-T cell therapy (EPIC) in relapsed or refractory multiple myeloma

Abstract

Abstract Introduction: Depth of response after idecabtagene vicleucel (ide-cel) CAR-T cell therapy has been correlated with longer progression-free survival in patients (pts) with relapsed or refractory multiple myeloma (R/R MM). BCMA-targeted bispecific antibodies have the potential to deepen responses after CAR-T cell therapy and reinvigorate polyclonal T cell responses against myeloma cells and improve CAR persistence. The EPIC trial is a single-arm, phase 2 study investigating elranatamab (Elra) as a consolidative, time-limited therapy after ide-cel with the goal of deepening and prolonging responses (NCT06138275). Methods: Eligible pts with R/R MM had received commercial ide-cel after 2 or more prior lines of therapy and could not have had PD after ide-cel prior to screening. Pts received fixed-duration Elra consolidation for 6 cycles starting between Day +100 and +160 after ide-cel. Elra schedule included the recommended step-up dosing followed by weekly dosing for cycle 1 and 2. Elra was administered every other week (days 1 and 15) for cycle 3-6. The primary endpoint is PFS. Secondary endpoints include adverse events, ORR, sCR/CR rate, DOR, OS, and analyses of MRD-negativity. Exploratory endpoints include changes in T-cell immunophenotype and soluble BCMA. Results: As of July 9, 2025, 16 pts have been enrolled and started Elra consolidation, and 8 pts (50%) have completed Elra consolidation. Among the enrolled pts, the median age was 68 years old (range: 48-82) and 56% were male. Five pts (31%) had history of high-risk cytogenetics [defined by t(4;14), t(14;16), or del(17p)] and/or TP53 mutation, 5 pts (31%) had R-ISS stage III disease, and 3 pts (19%) had history of extramedullary disease. Pts had received a median of 3 prior lines of therapy (range: 2-6) before ide-cel. The median time from ide-cel to start of Elra consolidation was 3.8 months (range: 3.0-5.2). Nine pts (56%) received step-up dosing as an outpatient. The median follow-up time for PFS from the start of consolidation was 5.4 months (range: 0.2-14.4; 9.1 months from ide-cel) among all enrolled pts and 10 months (range: 5.8-14.4; 13.7 months from ide-cel) among pts who have completed Elra consolidation. Among the 8 pts who had completed Elra consolidation, the majority (n=5/8, 63%) started Elra consolidation with ≤VGPR post-ide-cel, all of whom have had deepening of their disease response. Two pts (n=2/8, 25%) had deepening to sCR from SD or VGPR and 3 pts (n=3/8, 38%) had deepening to VGPR from PR. Six pts (n=6/8, 75%) had evaluable MRD samples at both screening and the end of Elra consolidation. Among the 6 MRD-evaluable pts, all pts (n=6/6, 100%) had MRD-positive disease at 10-6 sensitivity at screening and all pts (n=6/6, 100%) had conversion to MRD-negativity at 10-6 by the end of consolidation. Of the 3 pts (38%) who had evaluable MRD at 6 months after completing Elra consolidation, 2 pts had sustained MRD-negativity at 10-6and 1 pt was MRD-positive at 10-6but MRD-negative at 10-5. All patients are alive. One pt (n=1/16, 6.3%) has had progressive disease. This pt completed Elra consolidation in MRD-negative sCR and subsequently developed an isolated 1 cm subcutaneous plasmacytoma at 10.8 months from ide-cel (7.2 months from start of Elra consolidation). The plasmacytoma was managed with excision and radiation therapy. The pt has remained off systemic therapy without further progression at 18.5 months from ide-cel. Grade 1 CRS occurred in 5 pts (31%) and 1 pt received tocilizumab. There were no occurrences of ICANS or Grade ≥2 CRS. Grade 3 or 4 hematologic toxicity occurred in 5 pts (31%; Grade 3 anemia in 1 pt, Grade 3 or 4 neutropenia in 4 pts, Grade 4 thrombocytopenia in 1 pt). Grade 3 or 4 non-hematologic adverse events occurred in 6 pts (38%). Infections occurred in 8 pts (50%) with 2 pts (13%) having Grade 3 infections. Fourteen pts (88%) received IVIG. Conclusion: The phase 2 EPIC trial demonstrates that fixed-duration consolidation with Elra for 6 months can deepen disease response and improve MRD-negativity rates after ide-cel CAR-T cell therapy. Although the patients had received BCMA-directed CAR-T cells approximately 4 months prior to starting Elra, G3/4 infections were relatively infrequent (<15%). With a median follow-up time of 5.4 months, only one patient has had progressive disease. Longer follow-up and enrollment are ongoing to evaluate the PFS with Elra consolidation, and updated data will be presented.