Comparative effectiveness of teclistamab versus real-world treatments for patients with triple-class exposed (TCE), relapsed/refractory multiple myeloma (RRMM).

Abstract

8036 Background: Teclistamab is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in MajesTEC-1 (NCT04557098), an open-label, single-arm, phase 1/2 trial in patients with RRMM who had received ≥3 prior lines of therapy (LOT) and were TCE to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Given the absence of a control arm in MajesTEC-1, we assessed the comparative effectiveness of teclistamab versus treatment regimens using an external control arm from a real-world database. Methods: An external control arm for MajesTEC-1 was created from eligible patients in the nationwide de-identified electronic health record-derived Flatiron Health multiple myeloma cohort database who started a new line of therapy (physician’s choice) following triple-class exposure between January 2011 and August 2021, received ≥3 prior LOT, and satisfied key MajesTEC-1 eligibility criteria. Individual patient data from MajesTEC-1 included patients who received teclistamab (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline covariates of prognostic significance: refractory status, progression on last LOT, cytogenetic risk, International Staging System stage, number of prior LOT, time since diagnosis, age, and hemoglobin. Outcomes of interest included progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS); these outcomes were analyzed as time-to-event data using IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. Several sensitivity analyses were conducted. Results: After IPTW, baseline characteristics were comparable between the 2 cohorts. Patients treated with teclistamab had improved PFS (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.32–0.59; P< 0.0001), TTNT (HR 0.42; 95% CI 0.31–0.58; P< 0.0001), and OS (HR 0.73; 95% CI 0.48–1.09; P= 0.13) versus assessed real-world treatments. Results were similar for all sensitivity analyses. Conclusions: Teclistamab showed improved effectiveness for PFS, TTNT, and OS, compared with real-world treatments used in patients with TCE RRMM who received ≥3 prior LOT. These findings highlight the therapeutic potential of teclistamab in patients with RRMM who have limited treatment options.