Abstract Background and aims Isatuximab, a monoclonal antibody targeting CD38, has shown significant potential to improve outcomes in multiple myeloma (MM). However, its comparative efficacy and the specific impact on hematological and vascular toxicities across different treatment backbones require a comprehensive synthesis. This study evaluates the impact of isatuximab-based regimens on survival, depth of response, and safety profiles. Methods We systematically searched PubMed, Scopus, Web of Science, and Cochrane up to October 2025 for randomized controlled trials (RCTs) comparing isatuximab-based combinations to standard therapy. Data from the GMMG-HD7, ICARIA-MM, IKEMA, and IMROZ trials were pooled using a random-effects model. Results Four RCTs (n = 1,715) were included. Isatuximab-based regimens significantly improved PFS (HR 0.59; 95% CI: 0.47–0.73; P 0.00001) and were associated with a higher likelihood of achieving MRD negativity (RR 1.52; 95% CI: 1.18–1.96; P = 0.001). Regarding safety, isatuximab was associated with an increased incidence of grade 3 or higher neutropenia (RR 1.92; P = 0.02), thrombocytopenia (RR 1.22; P = 0.03), and respiratory infections (RR 1.46; P = 0.005). Crucially, no significant difference was observed in the risk of grade 3 or higher thromboembolic events (RR 1.11; 95% CI: 0.53–2.36; P = 0.78) or anemia (RR 0.94; P = 0.62). Conclusions The addition of isatuximab to standard myeloma backbones significantly improves survival and depth of response. While it increases the risk of high-grade hematological toxicities and respiratory infections, the lack of increased thromboembolic risk is a reassuring finding that supports isatuximab as a robust standard-of-care component in MM management. Conflict of interest All authors declare that they have nothing to disclose.
Elkoumi et al. (Fri,) studied this question.