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.