P-018: Updated Comparative Effectiveness of Talquetamab vs Real-World Physician’s Choice of Treatment in LocoMMotion and MoMMent for Patients With Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Introduction: Talquetamab (tal) is the first approved GPRC5D-targeting bispecific antibody for treatment of patients (pts) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) based on results from the MonumenTAL-1 study (NCT03399799/NCT04636552). LocoMMotion (NCT04035226) and MoMMent (NCT05160584) are two prospective, consecutive, observational studies evaluating real-world physician’s choice treatment (RWPC) in pts with TCE RRMM. Both studies were designed to mirror ongoing, single-arm trials to enable their use as external control arms. We report updated adjusted comparisons to determine the relative efficacy of tal vs RWPC.

Methods: Individual pt-level data (IPD) from MonumenTAL-1 were included for pts who received subcutaneous tal 0.4 mg/kg weekly (QW) or 0.8 mg/kg every other week (Q2W) (data cut-off [DCO] Jan 2024; median follow-up of 29.8 and 23.4 months, respectively). An external control arm was created using IPD from LocoMMotion (final data; median follow-up of 26.4 months) and MoMMent (DCO Aug 2023; median follow-up of 13.9 months) that met MonumenTAL-1 eligibility criteria. Imbalances in baseline characteristics were adjusted for using inverse probability of weighting with average treatment effect in the treated. Balance after adjustment was assessed using standardized mean differences (SMD). ORR, ≥VGPR, ≥CR, DOR, PFS, time to next treatment (TTNT), and OS outcomes were assessed. For binary outcomes, a weighted logistic regression was used to estimate odds ratios and response ratios with 95% CIs. For time-to-event outcomes, a weighted Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% CIs. Sensitivity analyses evaluated the impact of alternative statistical methods and variable adjustment.

Results: The RWPC cohort included 175 pts who met MonumenTAL-1 eligibility criteria, with 73 different treatment regimens. After weighting, the RWPC cohort was well balanced vs tal cohorts, with all SMD < 0.22. Pts who received tal QW (n=143) had superior outcomes vs RWPC: pts were 2.5, 4.5, and 95.8 times more likely to achieve a response (ORR), ≥VGPR, and ≥CR, respectively; had longer DOR (HR [95% CI], 0.72 [0.47–1.11]) and significantly longer TTNT (HR, 0.51 [0.39–0.67]; P< 0.0001); and had reduced risk for progression or death and death by 46% (P< 0.0001) and 62% (P< 0.0001), respectively. Similarly, pts who received tal Q2W (n=154) had superior outcomes vs RWPC: pts were 2.4, 4.8, and 124.0 times more likely to achieve a response (ORR), ≥VGPR, and ≥CR, respectively; had significantly longer DOR (HR, 0.49 [0.32–0.75]; P=0.001) and TTNT (HR, 0.44 [0.34–0.58]; P< 0.0001); and had reduced risk for progression or death and death by 54% (P< 0.0001) and 64% (P< 0.0001), respectively. Results were consistent across sensitivity analyses.

Conclusions: Tal QW and Q2W showed superior efficacy outcomes compared with RWPC with longer follow-up, highlighting its clinical benefit in pts with TCE RRMM.