Efficacy and safety of anti-CD38 monoclonal antibodies in patients with newly diagnosed multiple myeloma: an updated systematic review and meta-analysis based on randomized controlled trials

This meta-analysis of eight phase 3 RCTs assessed efficacy and safety of anti-CD38 monoclonal antibodies (mAbs) in patients with newly diagnosed multiple myeloma (NDMM). Anti-CD38 mAbs significantly improved progression-free survival (PFS: HR 0.50, 95% CI 0.42–0.59) and overall survival (OS: HR 0.63, 95% CI 0.55–0.71) in the overall population, alongside enhanced minimal residual disease (MRD) negativity rates (RR 1.85, 95% CI 1.43–2.39). While PFS benefits were universal across subgroups, OS showed no improvement in high-risk, ISS-I, or hepatic impairment subgroups, and non-IgG subtypes lacked MRD benefit. Safety analyses demonstrated an elevated risk of multiple infection-related adverse events in the entire cohort. The risk of second primary malignancies (SPMs) also increased (RR 1.44, 95% CI 1.14–1.81). Although anti-CD38 mAbs enhance treatment efficacy with manageable toxicity, the absence of OS benefit in high-risk subgroups warrants attention, and the risk of SPMs needs further investigation. PROSPERO registration number: CRD42024599221.