Use of CD38 antibodies in high-risk newly diagnosed multiple myeloma – meta-analysis

The anti-CD38 monoclonal antibodies daratumumab and isatuximab are both approved by the United States Food and Drug Administration for use in patients with newly diagnosed multiple myeloma (NDMM) in both the transplant-eligible and transplant-ineligible settings. However, the degree to which high-risk patients in particular benefit from the addition of an anti-CD38 monoclonal antibody to NDMM regimens is not clear. We conducted a meta-analysis to evaluate the effect of anti-CD38 monoclonal antibodies on progression free survival (PFS) using published randomized clinical trials completed in newly diagnosed multiple myeloma patients using these drugs. A total of 9 randomized trials were identified and included in the analysis. Frontline receipt of an anti-CD38 monoclonal antibody was associated with improved PFS both in patients with standard-risk NDMM (HR 0.51; 95% CI 0.46-0.58) and high-risk NDMM (HR 0.64, 95% CI 0.49-0.84). Similarly, the benefit was seen in standard risk and high risk NDMM in both the transplant and non-transplant trials as well. Overall, CD38 antibodies show improvement in progression free survival in patients with both standard and high-risk multiple myeloma.