Efficacy and Safety of Bispecific T-Cell Engagers in Relapsed/Refractory Multiple Myeloma: A Real-World Data-Based Case-Controlled Study.

Although bispecific T-cell engager (BiTE) is a promising treatment for relapsed/refractory multiple myeloma (RRMM), it needs to be evaluated in a real-world setting. This study aimed to evaluate the efficacy and safety of BiTEs compared with a synthetic standard of care (SOC). From a multicenter registry database of 474 patients with RRMM who received third- or more advanced-line treatments between January 2021 and October 2023, 1:1 propensity score-matched BiTE cohort (n = 71) and SOC cohort (n = 71) were established. Matching was based on age, sex, number of prior therapies, international staging system at diagnosis, and baseline biochemical characteristics. Compared with the matched SOC cohort, the matched BiTE cohort demonstrated a significant improvement in median progression-free survival (PFS, 19.2 vs 5.4 months, hazard ratio (HR) = .50 [95% CI, .33 to .78], p < .01). However, the overall survival (OS) was not significantly different between the two cohorts. Safety profiles showed that 37 (52%) patients in the matched BiTE cohort experienced cytokine release syndrome, mostly grade 1 (n = 29, 41%), with rare occurrences of neurotoxicity (n = 4, 5.6%). Infections were significantly more common in the matched BiTE cohort compared with the matched SOC cohort (81% vs. 49%, p < .01). Non-B-cell mutation antigen (BCMA)-targeted BiTEs improved 6-month OS rates compared with BCMA-targeted BiTEs in monotherapy (94% [95% CI, 84 to 100] vs. 65% [95% CI, 45 to 95], p = .04) and combination with daratumumab (100% [95% CI, 100 to 100] vs. 77% [95% CI, 57 to 100], p = .20). Non-BCMA-targeted BiTEs also provided benefit for 6-month PFS rate compared with the BCMA-targeted BiTE cohort in monotherapy (76% [95% CI, 59 to 100] vs. 50% [95% CI, 31 to 82], p = .11) and combination with daratumumab (100% [95% CI, 100 to 100] vs. 69% [95% CI, 48 to 99], p = .10). Quantitative bias and sensitivity analyses confirmed the robustness of these results. This real-world data-based study underscores the potential of BiTEs to significantly enhance survival outcomes in patients with heavily treated RRMM and manageable safety profiles. The difference in clinical outcomes by BiTE targets warrants further investigation in larger clinical trials (ClinicalTrials.gov identifier: NCT06205823).