(PA-006) Comparative Effectiveness of Teclistamab vs Real-world Physician’s Choice of Carfilzomib-and/or Pomalidomide-based Regimens in Locommotion and Momment in TCE RRMM

A pooled analysis from the prospective, noninterventional, multinational LocoMMotion (NeT04035226) and MoMMent (NeT05160584) studies demonstrated suboptimal outcomes in patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM), even when treated with carfilzomib and pomalidomide regimens. MajesTEC-1 (NCT04557098) is a single-arm phase 1/2 study evaluating teclistamab, a B-cell maturation antigen×CD3 (BCMA) bispecific antibody in patients with RRMM who are TCE. Here, we compared efficacy outcomes of patients who received teclistamab in MajesTEC-1 with those treated with carfilzomib and/or pomalidomide-based regimens in LocoMMotion and MoMMent pooled analysis.

Methods:   

An external control arm, Real-World Physician’s Choice (RWPC), was created from a pooled analysis of LocoMMotion (clinical cut-off: Oct 22) and MoMMent (clinical cut-off: Aug24) and compared with treated patients who met MajesTEC-1 eligibility criteria (teclistamab 1.5 mg/kg weekly; clinical cut-off: Aug 2023).

Inverse probability weighting was used to adjust for imbalances in baseline covariates. For binary endpoints such as overall response rate (ORR), relative effect of teclistamab versus RWPC was estimated with an odds ratio and relative response rate (RR) and 95% confidence interval (CI), derived from weighted logistic regression. Weighted Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% CIs for time-to-event endpoints [duration of response (DOR), progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS)].

Results:   

After reweighting, baseline characteristics were balanced across cohorts. Patients treated with Teclistamab in MajesTEC-1 had significant improvements in all evaluated efficacy outcomes.  Teclistamab-treated patients were almost 2-fold more likely to reach ORR (RR=2.10 (1.30 – 3.40), with durable responses DoR HR=0.31 (0.19-0.53) and longer TTNT HR=0.48 (0.36-0.66) compared with eligibility-matched patient cohorts treated with carfilzomib and/or pomalidomide in RWPC from the LocoMMotion/MoMMent pooled dataset. In addition Teclistamab demonstrated statistically significant improvements in PFS HR=0.50 (0.36-0.68) and OS HR=0.66 (0.47-0.93) vs this RWPC subgroup.

Conclusions:   

Teclistamab demonstrated improved effectiveness compared to the RWPC subgroup treated with carfilzomib and/or pomalidomide-based regimens, reinforcing its clinical value in delaying disease progression and extending the time to subsequent therapies in patients with TCE RRMM.