Abstract Topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Background: Talquetamab is a first-in-class G protein-coupled receptor family C group 5 member D × CD3 bispecific antibody. Talquetamab has shown an overall response rate (ORR) of ≥73% in patients with relapsed/refractory multiple myeloma (RRMM) who received ≥3 prior lines of therapy and were triple-class exposed (TCE) in the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552). Given the absence of head-to-head trials comparing talquetamab with other treatments, the comparative effectiveness of talquetamab vs other therapies can be done using indirect adjusted comparisons with real-world data to better direct future trial designs.
Aims: To evaluate the comparative effectiveness of talquetamab vs real-world physician’s choice (RWPC) treatment from the nationwide deidentified electronic health record-derived Flatiron Health MM cohort database study (Flatiron) in patients with TCE RRMM.
Methods: An external control arm for MonumenTAL-1 was created from eligible patients in the Flatiron database (data cut-off [DCO] Aug 2022) who satisfied key MonumenTAL-1 eligibility criteria (N=629 with 1169 eligible lines of therapy). Individual pt-level data from MonumenTAL-1 were included for patients who received talquetamab 0.4 mg/kg subcutaneously (SC) weekly (QW; N=143) and talquetamab 0.8 mg/kg SC every other week (Q2W; N=145) utilizing the Sept 2022 DCO. In the base model, baseline characteristics of prognostic variables (refractory status, cytogenetic risk, International Staging System stage, time to disease progression on the last line of therapy, number of prior lines of therapy, time since diagnosis, age, and hemoglobin) were adjusted using inverse probability of treatment weighting methodology. In addition to base model variables, a full model was also adjusted for prior stem cell transplant, ECOG performance status, race, sex, and MM type. Outcomes of interest were progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). For time-to-event outcomes, a weighted Cox proportional hazards model was used to derive hazard ratios (HRs), and a weighted Kaplan-Meier method was used to derive median time to event, each with their respective 95% CIs. Sensitivity analyses assessed the impact of alternative statistical methods and variable adjustment.
Results: Baseline characteristics were comparable after reweighting across all patient cohorts, with standardized mean differences <0.2. In the base model analysis, patients treated with both schedules of talquetamab 0.4 mg/kg QW (N=143) and 0.8 mg/kg Q2W (N=145) showed significantly improved outcomes vs RWPC (see Table). For the QW and Q2W schedule comparisons, the fully adjusted models remained in favor of talquetamab, consistent with the base model. Similar results for both schedule comparisons were also seen across the sensitivity analyses.
Summary/Conclusion: Both schedules of talquetamab demonstrated superior effectiveness vs RWPC treatment for all outcomes assessed. These data highlight the potential of talquetamab as an effective treatment option in patients with TCE RRMM and further support the rationale of planned prospective trials to compare talquetamab-based therapy and standard of care regimens in this patient population.
Keywords: G-protein-coupled receptors, Bispecific, Real world data, Multiple myeloma