P-056: Bispecific antibodies improve outcomes in patients with relapsed or refractory multiple myeloma after CAR-T cell therapy

Introduction: Despite the unprecedented rates of deep remissions in relapsed/refractory multiple myeloma (RRMM), virtually all patients experience relapse after CAR T-cell therapy. Although advances have been made in identifying risk factors for poor outcome after CAR T-cell therapy, the role of salvage treatments is uncertain. In the current study, we analyzed a large, international cohort of patients treated for relapse after BCMA-directed CAR T-cell therapies for RRMM.

Methods: We collected detailed data on disease-, treatment-, and patient-related factors of 12 centers from Europe and the United States. In addition, data on treatment sequences and responses were collected. Primary objective was to describe response to salvage practices for relapsed myeloma after CAR T and to identify regimen offering optimal outcomes.

Results: We included a cohort of 142 patients with relapse after commercial CAR T cell products who received salvage therapies. The median time from CAR T infusion to relapse/progression was 5 months (range, 0.4-33 months). 50% of patients experienced relapse with extramedullary disease (EMD). Patients received the following salvage treatments for first relapse/progression: Talquetamab (20%), Teclistamab (26%), combinations of IMiDs or CD38 monoclonal antibodies (31%), chemotherapy (11%), radiotherapy (4%), autologous or allogeneic transplant (3%), and others. Median time to first relapse was 5 months for the talquetamab group, 7 months for the teclistamab group, 4 months for the IMiDs/CD38 group, and 3 months for all others (P=0.04).

Response to first salvage treatment was significantly different, with talquetamab and teclistamab showing better responses (P< 0.001). Overall response rate was 77% for talquetamab, 62% for teclistamab, 26% for IMiDs/CD38, and 25% for the rest. Complete responses were seen in 32% of the talquetamab group, 33% of the teclistamab group, 3% of the IMiDs/CD38 group, and 0% of the rest. Very good partial responses were highest for talquetamab (27%), followed by teclistamab (15%).

Median follow-up of survivors after relapse was 8 months (95% CI, 7-9 months). Overall survival after relapse was significantly improved with bispecific antibodies (P< 0.001), showing 83% for talquetamab, 75% for teclistamab, 40% for IMiDs/CD38, and 23% for the rest at 8 months. Poorer prognosis was seen for EMD relapse with overall survival of 43% versus 67% for non-EMD relapse (P< 0.001) at 8 months. Importantly, both talquetamab and teclistamab appeared to be able to overcome the poorer prognosis of EMD relapse, showing promising survival and no significant difference between EMD vs non-EMD relapse (P=0.43 for talquetamab and P=0.86 for teclistamab).

Conclusions: Talquetamab and teclistamab improved outcomes for patients with relapse/progression after CAR T cell therapy. Both agents might overcome the dismal prognosis of EMD relapse. Final analyses including subgroups will be presented at the meeting.