Background: ELRA is a BCMAxCD3 bispecific antibody being investigated for the treatment of R/R MM. The phase 2 MM-3 trial was single-armed; the aim of this study (NCT05565391) was to contextualize the efficacy data from MM-3 with two real-world (RW) external control arms. Methods: A retrospective cohort study was conducted to indirectly compare the efficacy observed in MM-3 Cohort A (BCMA-naïve; N=123) from the 9-month data cut with two US-based oncology electronic health record databases, Flatiron Health (FH) and COTA, as external controls. MM-3 inclusion (eg, prior MM diagnosis, ECOG≤2, refractory to ≥1 PI, ≥1 IMiD, and ≥1 anti-CD38) and exclusion (I/E) criteria (eg, plasma cell leukemia, smoldering MM) were applied to each RW database to obtain comparable patient populations across sources. After imposing MM-3 I/E criteria, comparisons between data sources on ORR were conducted by estimating rate ratios (RRs) using log-binomial regression models (unweighted analysis). RRs were also estimated using both inverse probability treatment weighting (IPTW) and augmented IPTW (doubly robust) analyses to account for key covariates (eg, age, comorbidities, ECOG, ISS, prior lines/refractoriness, cytogenetic risk, extramedullary disease, lab values). Results: The 123 patients from MM-3 Cohort A were compared with the 152 and 233 patients identified from the FH and COTA databases, respectively. Treatment regimens in the RWD sources included various combinations of PIs, IMiDs, and mAbs, among other agents (eg, selinexor). Across unweighted, IPTW, and doubly robust analyses, the ORR for ELRA was significantly higher than treatments used for TCR MM patients from RWD sources (Table; all p<.05). Conclusions: Among TCR MM patients who resemble those of the MM-3 trial, ELRA showed improved ORR compared with treatments currently used in clinical practice.

FH, Flatiron Health; CI, confidence interval; ORR, objective response rate; RR, rate ratio.*Some patients were excluded from the IPTW and doubly robust analyses due to missing values for variables used in the propensity score model.