Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens

The incorporation of CD38-targeted monoclonal antibodies into induction therapy has improved outcome in patients with newly diagnosed multiple myeloma (NDMM), yet the benefit across risk subgroups remains controversial. We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies (daratumumab or isatuximab) and assessed the efficacy and safety of anti-CD38-based induction regimens in NDMM. Primary outcomes were minimal residual disease (MRD)-negativity and progression-free survival (PFS). Eleven trials encompassing 5588 patients, including 915 with high-risk multiple myeloma (HRMM), were included. Anti-CD38-containing regimens significantly increased MRD-negativity in both transplant-eligible (TE; pooled odds ratio [OR], 2.32; 95% confidence interval [CI], 1.74-3.11) and transplant-ineligible (TIE; pooled OR, 3.26; 95% CI, 2.20-4.84) patients. Among TE patients, MRD-negativity improved in both HRMM (pooled OR, 2.01; 95% CI, 1.41-2.88) and standard-risk MM (pooled OR, 2.74; 95% CI, 1.99-3.84). Anti-CD38 therapy also significantly prolonged PFS in TE (pooled hazard ratio [HR], 0.52; 95% CI, 0.38-0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49-0.61), with an overall survival benefit observed in TIE patients. PFS improvement was consistent across cytogenetic risk and clinical subgroups. Grade 3 or 4 infections and hematologic toxicities occurred more frequently with anti-CD38 regimens. In summary, anti-CD38-based induction improves depth of response and PFS across NDMM populations, including high-risk disease, with increased but manageable toxicity.