Background: Bispecific antibodies (BsAb) and Chimeric antigen receptor T-cell therapy (CAR-T) have significantly transformed treatment landscape for patients with relapsed, refractory multiple myeloma (RRMM) after four or more prior lines of therapy. Despite these advances, the efficacy of BsAbs and CAR-T—particularly overall response rate (ORR) and progression-free survival (PFS) in patients with extramedullary disease (EMD) and high-risk cytogenetic abnormalities (HRCA) remains incompletely characterized. The purpose of this systematic review and meta-analysis is to compare the ORR and PFS for BsAbs vs CAR-T therapies in the treatment of EMD and HRCAs in RRMM.

Methods:

A systematic literature search was conducted to identify clinical trials that investigated BsAbs and CAR-T therapies in treating RRMM patients using the PubMed, Cochrane, and abstracts from ASH (through 2024), ASCO (through 2025), and EHA (through 2025). Search terms included (bispecific antibodies) AND (multiple myeloma), (CAR T cell therapy) AND (multiple myeloma). ORR and PFS rates were the outcome variables of interest, reported for the overall group and for subgroups based on EMD and HRCA. R-Studio Desktop Version 2023.03.0+ 386 was used for statistical analysis. Cochrane-Q test and I² statistic were used to assess the statistical heterogeneity. A fixed effect model was used for low heterogeneity (P > 0.05 in Cochrane-Q test and I² < 50%), while a random effect model was used for high heterogeneity (P < 0.05 in Cochrane-Q test and I² > 50%). Categorical outcomes were summarized by pooled proportion with 95% Confidence intervals (CI).

Results Bispecific antibodies (BsAbs) ORR was reported in 1181 study patients across 11 studies, and 12-month PFS was reported for 233 participants in 8 studies. For EMD, ORR was reported in 8 studies (n=233), and for HRCA, in 7 studies (n=245). The pooled ORR among all patients treated with BsAbs was 0.64 [95% CI: 0.58 to 0.69]. The pooled ORR for EMD was 0.54 [95% CI: 0.38 to 0.70], and for HRCA, 0.66 [95% CI: 0.60 to 0.71]. The pooled response proportion for triple class refractory cases was 0.67 [95% CI: 0.62 to 0.71], and for penta-class refractory was 0.65 [95% CI: 0.59 to 0.70]. Funnel plot analysis is symmetrical, indicating no probability of publication bias for ORR for BsAbs with a p-value of 0.676. The pooled PFS at 12 months with BsAbs was 0.54 (95% CI: 0.38 to 0.70).

CAR T cell therapy ORR was reported across 9 studies with a pooled sample size of 1085. For EMD and HRCA, ORR was reported in 8 studies (n=233) and 7 studies (n=245), respectively. The pooled ORR for CAR T was 0.86 [95% CI: 0.76 to 0.95]. The pooled proportion of ORR in MM patients with EMD and HRCAs was 0.76 [95% CI: 0.56 to 0.95] and 0.77 [95% CI: 0.64 to 0.91] respectively. The pooled response proportion to triple class refractory was 0.79 [95% CI: 0.59 to 0.98], and penta-class refractory was 0.76 [95% CI: 0.53 to 0.99]. The pooled 12-months PFS with CAR-T was 0.57 (95% CI: 0.39 to 0.76).

Conclusion: To our knowledge, this is the first systematic review and meta-analysis that provides the most recent pooled analysis of both PFS and ORR in EMD and HRCA. Consistent with prior analyses, CAR T cell therapy shows higher ORR in the whole cohort, as well as in EMD and HRCA subgroups, while PFS at 12 months appears similar between the CAR-T and BsAbs. Direct comparisons are limited by underlying heterogeneity and differences between studies. More consistent reporting of PFS and ORR in published clinical data is essential to accurately determine the true effect size. Further analysis incorporating real-world data is ongoing.

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2025
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