OA-31: Efficacy of Bispecific Antibodies in the Treatment of Extramedullary disease and High risk cytogenetics in Relapsed Multiple Myeloma: A Systematic Review

Introduction: Bispecific antibodies (BsAbs) are effective treatments for relapsed multiple myeloma (MM). The purpose of this systematic review is to determine the efficacy of BsAbs in the management of extramedullary disease (EMD) and high risk cytogenetic abnormalities (HRCAs) in relapsed MM.

Methods: A systematic literature search was conducted to identify clinical trials that investigated BsAbs in MM using the PubMed database and ASH-submitted abstracts using search terms (bispecific antibodies) AND (multiple myeloma). Our search on PubMed yielded 263 studies, of which 7 were clinical trials; of these, 5 were included, and 6 ASH abstracts were included. Cochrane-Q test and I² statistic were used to assess the statistical heterogenicity. A fixed effect model was used for low statistical heterogeneity (P > 0.05 in Cochrane-Q test and I² < 50%), while a random effect model was used for high statistical heterogeneity (P < 0.05 in Cochrane-Q test and I² > 50%). Categorical outcomes were summarized by pooled proportion with 95% CI.

Results: Overall response rates (ORRs) of the entire cohort were reported in 660 patients across 9 studies. The ORRs for EMD and HRCAs were reported in 3 (n=78) and 4 (n=100) studies, respectively. The ORR of the entire cohort was 0.65 [95% CI; 0.57; 0.74). The ORR of each BsAb was 0.70 (0.51-0.85; Chari et al, 2022) for talquetamab, 0.63 (0.55-0.70; Moreau et al, 2022) for teclistamab, and 0.61 (0.52-0.70; Bahlis et al, 2022) for elranatamab.

The ORRs in MM with EMD and HRCAs with 95% CI were 0.38 [0.28; 0.49] and 0.60 [0.51; 0.70], respectively. Among the studies that reported the ORR in EMD, talquetamab (Chari et al, 2022) has the highest ORR of 0.45 (0.17; 0.77), followed by elranatamab (Bahlis et al, 2022) of 0.38 (0.23; 0.55), and teclistamab (Moreau el al, 2022) of 0.36 (0.19; 0.56). There is no significant difference in the ORR between the drugs with respect to EMD status.

In studies that reported the ORR in HRCAs, talquetamab (Chari et al, 2022) had an ORR of 0.67 (0.17; 0.77) followed by teclistamab (Moreau el al, 2022) of 0.61 (0.43; 0.76), and elranatamab (Bahlis et al, 2022) of 0.55 (0.36; 0.73). Similarly, there is no significant difference in the ORR between the drugs with respect to HRCA status.

The above results demonstrate that ORR in EMD is lower when compared to the entire cohort.

Conclusions: Despite 11 clinical trials done with bispecific antibodies only 4 had reported EMD responses. This needs to be improved and clinical trials should report EMD responses distinctly as it directly informs clinical decisions. EMD responses are significantly lower than the full cohort ORR however it is encouraging that responses to high risk multiple myeloma (HRMM) closely approximate ORR of these agents. Further analysis is needed to see whether ORR and PFS correlate for HRMM. Evidence was insufficient to establish the relative superiority of one BsAb over another with EMD and combination therapies should be explored for EMD in myeloma.