Efficacy of Teclistamab vs Real-World Treatments for Patients with Triple-Class Exposed, Relapsed/Refractory Multiple Myeloma

The agent teclistamab is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in MajesTEC-1 (NCT04557098) which is an open-label, single-arm, phase 1/2 trial in patients with relapsed/refractory multiple myeloma (RRMM) who had received 3 or more prior lines of therapy (LOT) and were triple-class exposed (TCE) to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. 

Dr Amrita Y Krishan, City of Hope Comprehensive Cancer Center, Duarte, CA and colleagues evaluated the comparative effectiveness of teclistamab vs treatment regimens using an external control arm from a real-world database since there is an absence of a control arm in MajesTEC-1 trial.

In the study, researchers created an external control arm for MajesTEC-1 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 or more 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 employed 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 evaluated as time-to-event data utilizing IPTW adjusted Kaplan-Meier estimates and a weighted Cox proportional hazards model. The researchers conducted numerous sensitivity analyses. 

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. For all sensitivity analyses, results were comparable. 

The authors concluded that the usage of teclistamab demonstrated enhanced effectiveness for PFS, TTNT, and OS, compared with real-world treatments employed in patients with TCE RRMM who received 3 or more prior LOT. They also noted that in patients with RRMM who have limited treatment options, these findings emphasize the therapeutic potential of teclistamab.

Reference

Krishnan A, Nooka A, Chari A, et al. Comparative effectiveness of teclistamab versus real-world treatments for patients with triple-class exposed (TCE), relapsed/refractory multiple myeloma (RRMM). Abstract presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, and virtual. Abstract 8036.