Abstract
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.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.Eleven RCTs comprising 5,588 patients (915 HRMM) were included. Among them, 2,874 received anti-CD38 antibody–containing regimens, while 2,714 received the same backbone without antibody. Addition of anti-CD38 antibodies significantly increased MRD negativity in both transplant-eligible (TE) (pooled odd ratio [OR], 2.32; 95% CI, 1.74–3.11) and transplant-ineligible (TIE) (pooled OR, 3.26; 95% CI, 2.20–4.84) NDMM. Stratified analysis in TE NDMM showed improved MRD negativity in HRMM (pooled OR, 2.01; 95% CI, 1.41–2.88) and standard-risk MM (SRMM) (pooled OR, 2.74; 95% CI, 1.99–3.84). Anti-CD38 therapy also significantly prolonged PFS in TE NDMM (pooled HR, 0.52; 95% CI, 0.38–0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49–0.61), with overall survival (OS) benefit observed in TIE patients. Subgroup analyses indicated consistent PFS improvement across cytogenetic risk, age, performance status, International Staging System (ISS) stage, and renal function. Safety analysis demonstrated increased grade 3–4 infections (pooled OR, TE: 1.30; TIE: 1.58), neutropenia (pooled OR, 1.85), and thrombocytopenia (pooled OR, 1.34) with anti-CD38 therapy.Our findings suggest that the addition of anti-CD38 monoclonal antibody to induction regimens in NDMM significantly improve MRD negativity and PFS across risk groups and patient populations but are associated with increased hematologic and infectious toxicities. These findings support the use of anti-CD38 therapy in both TE and TIE NDMM, while careful monitoring for adverse events is warranted.
Author notes
These authors contributed equally to this work.
Yongqiang Wei and Xiaolei Wei are co-senior authors.
Data Availability
The data supporting this meta-analysis are derived from published randomized clinical trials listed in the References section. All extracted datasets and statistical codes used for analysis are available from the corresponding author upon reasonable request. No new raw data were generated in this study.
