Comparative Efficacy of Talquetamab vs. Current Treatments in the LocoMMotion and MoMMent Studies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma

Abstract

[EN] Introduction: Talquetamab, a bispecific antibody targeting GPRC5D 9 CD3, is approved for the treatment of patients with triple-class - exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phase I/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. realworld physician’s choice of therapy (RWPC) was assessed using adjusted comparisons. Methods: An external control arm for MonumenTAL- 1 (subcutaneously administered talquetamab 0.4 mg/kg weekly [QW] and 0.8 mg/ kg every other week [Q2W]) was created from two observational real-world studies: LocoMMotion and MoMMent. Imbalances in baseline covariates were adjusted using inverse probability weighting. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), C very good partial response (VGPR), and C complete response (CR); odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional hazards model. Results: After reweighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, patients treated with talquetamab QW (n = 143) had significantly improved outcomes vs. RWPC; RRs were ORR 2.67, p\0.0001; C VGPR 4.70, p\0.0001; C CR 78.05, p = 0.0002; and HRs were PFS 0.52, p\0.0001; TTNT 0.48, p\0.0001; OS 0.36, p\0.0001. Patients treated with talquetamab Q2W (n = 145) also had significantly improved outcomes vs. RWPC; RRs were ORR 2.62, p\0.0001; C VGPR 5.04, p\0.0001; C CR 101.14, p = 0.0002; and HRs were PFS 0.40, p\0.0001; TTNT 0.39, p\0.0001; OS 0.37, p\0.0001. Conclusion: Effectiveness of talquetamab for both schedules was significantly better than RWPC for ORR, C VGPR, C CR, PFS, OS, and TTNT, highlighting its clinical benefit for patients with TCE RRMM. Trial Registration: MonumenTAL-1, ClinicalTrials. gov identifier NCT03399799/ NCT04634552; LocoMMotion, ClinicalTrials.- gov identifier NCT04035226; MoMMent, ClinicalTrials. gov identifier NCT05160584. Keywords: LocoMMotion; MoMMent; MonumenTAL-1; Talquetamab; Triple-classexposed relapsed/refractory multiple myeloma