PB2014: TECLISTAMAB VS SELINEXOR-DEXAMETHASONE IN PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA: A MATCHING-ADJUSTED INDIRECT COMPARISON

Abstract

Background: Teclistamab, is a B-cell maturation antigen × CD3 bispecific antibody. MajesTEC-1 (NCT04557098), a single-arm, phase 1/2 study evaluating teclistamab in patients with RRMM who were exposed to at least 3 lines of therapy (LOT), comprising a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Though there is currently no standard of care for patients with triple-class exposed (TCE) RRMM, selinexor-dexamethasone (sel-dex) is a recently approved, novel therapeutic option. Aims: An unanchored matching-adjusted indirect comparison (MAIC) was conducted to compare efficacy results of patients treated with teclistamab in MajesTEC-1 with those treated with sel-dex in the single-arm, phase 2b STORM Part 2 study (NCT02336815). Methods: Individual patient-level data (IPD) collected from 150 patients treated with 1.5 mg/kg weekly teclistamab from MajesTEC-1 (Sep 7, 2021 data cut) and published summary-level data from 122 patients treated with sel-dex in the STORM Part 2 study were used in the unanchored MAIC. Eligibility criteria from STORM Part 2 (triple-class refractory, penta-exposed, and refractory to last LOT) were applied to patients in the MajesTEC-1 trial. The resulting IPD from 69 patients from the MajesTEC-1 trial were then weighted to match the aggregated baseline characteristics of patients from STORM Part 2. Baseline characteristics of prognostic significance were cytogenetic profile, presence of extramedullary disease, refractory status, revised International Staging System stage, and number of prior LOT; all were adjusted for in the analysis. Overall response rate (ORR), complete response or better (≥CR) rate, progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were estimated to compare efficacy between teclistamab and sel-dex. For binary endpoints (ORR and ≥CR rate), odds ratio (OR) and 95% confidence interval (CI), derived from a weighted logistic regression, were used to estimate relative effects of teclistamab vs sel-dex. A weighted Cox proportional hazards model was used to estimate time-to-event endpoints (PFS, OS, and DOR). Results: Baseline characteristics were balanced between the 2 cohorts. The effective sample size (ESS) of the MajesTEC-1 cohort was 37 after adjustment. Improved ORR (OR 3.14; 95% CI 1.48–6.69; P=0.0029), ≥CR rate (OR 16.3; 95% CI 3.5–77.1; P=0.0004), PFS (HR 0.58; 95% CI 0.30–1.11; P=0.1007), DOR (hazard ratio [HR] 0.04; 95% CI 0.01–0.10; P<0.0001), and OS (HR 0.52; 95% CI 0.28–0.95; P=0.0344) were observed in patients treated with teclistamab versus those treated with sel-dex. The majority of outcomes in favor of teclistamab were significant (P<0.05), despite a reduced ESS which limited power to detect statistically significant differences. Summary/Conclusion: Teclistamab significantly improved efficacy over sel-dex for all outcomes except PFS (though numerically in favor of teclistamab) in this MAIC. These findings highlight the potential of teclistamab as a highly effective treatment option for patients with TCE RRMM who received at least 3 prior LOT.