Addition of anti-CD38 monoclonal antibody in newly diagnosed multiple myeloma: Advancing toward quadruplet induction regimens? A Systematic Review and Meta-Analysis

Background: The addition of CD38-targeted monoclonal antibodies, such as daratumumab and isatuximab, to standard treatment regimens has been shown to improve progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM). However, the benefits in specific subgroups, particularly high-risk multiple myeloma (HRMM) defined by cytogenetic abnormalities, remain controversial. Method: 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 in NDMM. A meta-analysis was performed to evaluate the minimal residual disease (MRD)-negative status rate and PFS, stratified by cytogenetic risk. Result: A total of 5193 patients (863 patients were HRMM) in 10 randomized clinical trials were included. Of these, 2,677 patients received induction regimens containing anti-CD38 monoclonal antibody, while 2,516 were treated with the same backbone regimens without the antibody. The addition of anti-CD38 monoclonal antibody significantly increased the MRD-negative status rate in both transplant-eligible (TE) NDMM patients (pooled odds ratio [OR], 2.31; 95% confidence interval [CI], 1.72–3.10) and transplant-ineligible (TIE) NDMM patients (pooled OR, 3.51; 95% CI, 2.18–5.67). Furthermore, the MRD-negative status rates improved for both HRMM (pooled OR, 2.01; 95% CI, 1.39–2.91) and standard-risk multiple myeloma (SRMM) patients (pooled OR, 2.93; 95% CI, 1.87–4.58). Additionally, PFS was markedly enhanced in patients treated with anti-CD38 antibody compared to those receiving backbone regimens alone, for both TE NDMM patients (pooled hazard ratio [HR], 0.52; 95% CI, 0.38–0.69) and TIE NDMM patients (pooled HR, 0.52; 95% CI, 0.43–0.62). Subgroup analyses indicated similar PFS benefits for both HRMM (pooled HR, 0.61; 95% CI, 0.42–0.90) and SRMM patients (pooled HR, 0.38; 95% CI, 0.28–0.52). Conclusion Our findings suggest that the addition of anti-CD38 monoclonal antibody to induction regimens enhances the MRD-negative status rate and improves PFS in NDMM patients, regardless of cytogenetic risk.