P923: 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

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Talquetamab (tal) is a G protein-coupled receptor family C group 5 member D × CD3 bispecific antibody. In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04636552), tal has shown an overall response rate (ORR) of ≥73% in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who have received ≥3 prior lines of therapy (LOT) and are triple-class exposed (TCE). LocoMMotion (NCT04035226) and MoMMent (NCT05160584) are prospective observational studies characterizing real-world physician’s choice (RWPC) treatment and associated clinical outcomes in pts with TCE RRMM recruited between 2019 and 2022. In the absence of a control arm in MonumenTAL-1, adjusted comparisons can be performed to determine the relative effectiveness of tal vs other treatments. Aims: To contextualize the comparative effectiveness of talquetamab vs RWPC in pts with TCE RRMM. Methods: Individual pt-level data (IPD) from MonumenTAL-1 were included for pts who received tal 0.4 mg/kg subcutaneously (SC) weekly (QW) and tal 0.8 mg/kg SC every other week (Q2W) utilizing the Sept 2022 data cut-off (DCO) date. An external control arm was created using IPD from LocoMMotion and MoMMent (both DCO Oct 2022) who met MonumenTAL-1 eligibility criteria. Imbalances in baseline characteristics of prognostic variables (refractory status, ISS stage, time to progression on prior LOT, extramedullary disease, number of prior LOT, time since diagnosis, average duration of prior LOTs, age, hemoglobin, lactate dehydrogenase, creatinine clearance, ECOG performance status, sex, MM type, and prior stem cell transplant) were adjusted for using inverse probability of weighting (IPW) with average treatment effect in the treated (ATT) weights applied to the RWPC cohort to balance versus the two tal cohorts separately. Balance after adjustment was assessed using standardized mean differences (SMD). Outcomes of interest were ORR, ≥VGPR, ≥CR, DOR, PFS, time to next treatment (TTNT), and OS. Response and progression outcomes were evaluated based on IMWG criteria. For binary outcomes, a weighted logistic regression was used to estimate odds ratios and response ratios (RRs) with the respective 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 (alternative weighting approaches and multivariable regression). Results: From the pooled RWPC cohort, 177 pts fulfilled the inclusion criteria. At baseline, pts received 58 different treatment regimens. After weighting, the RWPC cohort was well balanced versus both tal cohorts, with all SMD <0.20. Pts treated with tal 0.4 mg/kg QW (N=143) had superior outcomes vs RWPC (see Table): pts were 2.6, 5.3, and 95.3 times more likely to achieve response (ORR), ≥VGPR, and ≥CR, respectively, and had reduced risk for progression or death and death by 47% and 56%, respectively. Similarly, pts treated with tal 0.8 mg/kg Q2W (N=145) had superior outcomes vs RWPC (see Table): pts were 2.6, 5.0, and 106.8 times more likely to achieve response (ORR), ≥VGPR, and ≥CR, respectively, with significantly longer DOR, and had reduced risk for progression or death and death by 57% and 56%, respectively. Results were generally consistent across all sensitivity analyses. Summary/Conclusion: Both schedules of tal showed superior effectiveness compared with RWPC, highlighting its clinical benefit and novel treatment option for pts with TCE RRMM.Keywords: Bispecific, G-protein-coupled receptors, Multiple myeloma, Real world data