BCMA/CD19 dual-targeting CAR T cell therapy in older patients with newly diagnosed multiple myeloma: a phase I study

GC012F, now renamed AZD0120, is an autologous B-cell maturation antigen (BCMA) and CD19 dual-targeting CAR T cell product manufactured on the novel FasTCAR® platform. CAR T cell therapy has not been routinely studied in older patients with newly diagnosed multiple myeloma (NDMM). Therefore, we conducted a trial to assess AZD0120 as a frontline therapy for MM patients age ≥70. In this single-arm phase 1 study, NDMM patients age ≥70 received two cycles of VRD (bortezomib/lenalidomide/dexamethasone) induction therapy followed by AZD0120 infusion at the dose of 1.5x105 or 3x105 cells/kg. A total of 8 patients received AZD0120, with 4 classified as frail according to the Intergroupe Francophone du Myelome Simplified Frailty Score criteria, while the remaining 4 were non-frail patients. At a median follow-up of 9.8 months post-infusion, hematologic toxicities being the most common ≥grade 3 treatment-emergent adverse events (TEAEs), including lymphopenia (25%), leukopenia (50%), and neutropenia (75%). Four (50%) patients had cytokine release syndrome (CRS), all grade 1. No immune effector cell-associated neurotoxicity syndrome (ICANS) was observed. All patients achieved stringent complete response (sCR) and all patients achieved minimal residual disease (MRD) negativity by Euroflow (10-6) at 1 month, with MRD negativity rates of 100% among evaluable patients at month 6 (n=7) and month 12 (n=2). Two patients in the frail subgroup with ECOG status of 2 recovered to ECOG status of 1 post-infusion. AZD0120 dual-targeting fast CAR T shows promising preliminary efficacy and a manageable safety profile for older patients with NDMM. NCT05840107.