PB2013: TECLISTAMAB COMPARED WITH REAL-WORLD THERAPIES IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA

Abstract

Background: Teclistamab is a B-cell maturation antigen × CD3 bispecific antibody that promotes T cell activation by redirecting CD3+ T cells, resulting in lysis of BCMA-expressing myeloma cells. MajesTEC-1 (NCT04557098) is an open-label, single-arm, phase 1/2 trial of teclistamab in patients with relapsed/refractory multiple myeloma (RRMM) who had received at least 3 prior lines of therapy (LOT) and were triple-class exposed (TCE) to a proteasome inhibitor, an anti-CD38 monoclonal antibody, and an immunomodulatory agent. Aims: Because MajesTEC-1 did not include a control arm, comparative effectiveness of teclistamab versus treatment regimens using an external control arm from a real-world database was evaluated. Methods: The external control arm was created using eligible patients in the nationwide Flatiron Health multiple myeloma database, which was derived from de-identified electronic health records. Patients comprising the external control arm had received ≥3 prior LOT, started a new LOT per physician’s choice after triple-class exposure between January 2011 and August 2021, and met key MajesTEC-1 eligibility criteria. Individual patient data were included from patients who had been treated with 1.5 mg/kg weekly teclistamab in the MajesTEC-1 at the Sep 7, 2021 clinical cutoff. Imbalances in baseline covariates of prognostic significance (refractory status, number of prior LOT, progression on last LOT, International Staging System stage, cytogenetic risk, time since diagnosis, age, and hemoglobin), were adjusted by using inverse probability of treatment weighting (IPTW). Progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were outcomes of interest, and were analyzed as time-to-event data utilizing IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. Several sensitivity analyses were also performed. Results: The two cohorts were comparable for baseline characteristics after IPTW. Teclistamab 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) compared with real-world treatments. Sensitivity analyses showed results were also consistent with these findings. Summary/Conclusion: In patients with TCE RRMM who received at least 3 prior LOT, teclistamab showed improved effectiveness for PFS, TTNT, and OS versus real-world treatments, highlighting the therapeutic potential of teclistamab for patients with RRMM.