Real-world comparison of anti-BCMA vs anti-GPRC5D BiTE therapy in relapsed/refractory multiple myeloma without prior CAR-T cell exposure.

7542 Background: In recent years, three bispecific T-cell engager (BiTE) agents have been approved for Refractory/Relapsed Multiple Myeloma (rrMM). These have shown remarkable efficacy, particularly in patients who have failed multiple lines of prior therapy. However, there is a paucity of data to guide choice between available agents. Methods: We performed a multicenter, retrospective, propensity score matched (PSM), safety and efficacy comparison between anti-BCMA (Cohort 1: Teclistamab and Elranatamab) and anti-GPRC5D (Cohort 2: Talquetamab) therapy in rrMM, using TriNetX database. Patients with prior CAR-T therapy were excluded. Outcomes assessed included survival, remission rates, subsequent CAR-T therapy, subsequent alternate BiTE therapy, risk of infections, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hypogammaglobulinemia and IVIG use with a follow up of 2 years following treatment. Results: A total of 888 and 296 patients were identified in cohort 1 (C1) and cohort 2 (C2), respectively. The two cohorts were matched for 25 characteristics yielding 266 patients in the PSM analysis. No differences in survival probability (HR 0.95; 95% CI 0.65-1.39, p=0.83) or remission rates (C1 vs C2: 37.2 vs 35.0 %, p=0.588) were observed. Subsequent CAR-T therapy was used in 3.8% in C1 and 15% of patients in C2. Any grade CRS (C1 vs C2: 34.6 vs 48.1%, p=0.002) was more common in the Talquetamab cohort, with majority being grade<3 CRS (C1 vs C2: 16.2 vs 27.8%, p=0.001). There was no difference observed for any grade ICANS (C1 vs C2: 14.7 vs 9.8%, p=0.08). No significant differences were found between rates of overall infection (C1 vs C2: 45.5 vs 43.6 %, p=0.63), bacterial (C1 vs C2: 23.3 vs 21.1%, p=0.53), viral (C1 vs C2: 28.6 vs 28.2 %, p=0.92), or fungal (C1 vs C2: 5.8 vs 8.9 %, p=0.29) infections rates. The incidence of hypogammaglobulinemia (C1 vs C2: 74.4 vs 77.8%, p=0.36) and treatment with IVIG (C1 vs C2: 52.3 vs 44.4 %, p=0.06) were similar across both groups. Conclusions: Our analysis of real-world patients with relapsed/refractory multiple myeloma (rrMM) showed similar efficacy and tolerability between anti-BCMA and GPRC5D BiTE therapies. However, the Talquetamab group had a higher rate of CRS, consistent with the high incidence observed in the phase 2 MonumenTAL-1 trial. The extent of comorbidities, safety profile of individual agents and plan for subsequent CAR-T cell therapy can guide the choice between available BiTE therapies. BiTE therapy: Demographics and outcomes. Outcome Cohort 1 Cohort 2 p-value Total # of pts 266 266 Mean Age (years) 67.2 67.4 0.82 Male/Female (%) 52.6 / 43.6 50.4 / 43.2 0.60/0.93 Mean duration of treatment (Days) 246 (Teclist)163 (Elra) 182 2-yr Survival 55 (54.5%) 53 (50.6%) 0.76 Complete Remission 99 (37.2%) 93 (35.0 %) 0.59 CRS 92 (34.6%) 128 (48.1%) 0.002