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Use of CD38 Antibodies in High-Risk Newly Diagnosed Multiple Myeloma: A Meta-Analysis
Divaya Bhutani1, Yusha Liu2, Rajshekhar Chakraborty1
1Division of Hematology Oncology, Columbia University Medical Center, New York, NY.
The anti-CD38 monoclonal antibodies Daratumumab and Isatuximab are both approved for use in patients with newly diagnosed multiple myeloma (NDMM) in both the transplant-eligible and transplant-ineligible setting. 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. In this meta-analysis we analyzed data from a total of 9 prospective clinical trials (MAIA, ALCYONE, CEPHEUS, IMROZ, OCTANS, CASSIOPEIA, GRIFFIN, PERSEUS, and GMMG-HD7) to evaluate benefit of CD38 antibodies in both standard and high-risk patients. 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). Subgroups of patients with standard-risk disease derived similar benefit from frontline anti-CD38 monoclonal antibody use, whether in a nontransplant study (HR 0.49, 95% CI, 0.43-0.57) or transplant study (HR 0.52, 95% CI, 0.40-0.67). Subgroups of patients with high-risk disease also benefitted, although somewhat more for those treated on transplant studies (HR 0.57, 95% CI, 0.35-0.94) than those treated on nontransplant studies (HR 0.71, 95% CI, 0.53-0.97). Patients with high-risk NDMM and standard-risk NDMM treated on frontline myeloma trials experienced improved PFS with anti-CD38 monoclonal antibody-based regimens, although the effect was less pronounced in high-risk patients treated on nontransplant studies.
The anti-CD38 monoclonal antibodies Daratumumab and Isatuximab are both approved for use in patients with newly diagnosed multiple myeloma (NDMM) in both the transplant-eligible and transplant-ineligible setting. 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. In this meta-analysis we analyzed data from a total of 9 prospective clinical trials (MAIA, ALCYONE, CEPHEUS, IMROZ, OCTANS, CASSIOPEIA, GRIFFIN, PERSEUS, and GMMG-HD7) to evaluate benefit of CD38 antibodies in both standard and high-risk patients. 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). Subgroups of patients with standard-risk disease derived similar benefit from frontline anti-CD38 monoclonal antibody use, whether in a nontransplant study (HR 0.49, 95% CI, 0.43-0.57) or transplant study (HR 0.52, 95% CI, 0.40-0.67). Subgroups of patients with high-risk disease also benefitted, although somewhat more for those treated on transplant studies (HR 0.57, 95% CI, 0.35-0.94) than those treated on nontransplant studies (HR 0.71, 95% CI, 0.53-0.97). Patients with high-risk NDMM and standard-risk NDMM treated on frontline myeloma trials experienced improved PFS with anti-CD38 monoclonal antibody-based regimens, although the effect was less pronounced in high-risk patients treated on nontransplant studies.