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Adding a CD38 antibody to the standard three-drug induction roughly halves progression risk in newly diagnosed myeloma.
Adding a CD38 antibody, daratumumab or isatuximab, to the proteasome inhibitor, immunomodulatory drug and dexamethasone triplet creates the quadruplet induction now standard for newly diagnosed multiple myeloma whether or not a transplant is planned. The drug classes act through non-overlapping mechanisms: bortezomib imposes proteasome stress, lenalidomide drives cereblon-mediated degradation, and the CD38 antibody adds Fc-mediated plasma-cell killing with immunomodulation. Four positive phase 3 trials support it, PERSEUS with daratumumab-VRd around transplant, CEPHEUS, IMROZ with isatuximab-VRd, and MAIA with daratumumab-Rd in older patients, and MAIA also showed an overall survival benefit. Across these trials the quadruplet sharply reduced the risk of progression.
PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Shares CEPHEUS, IMROZ, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Daratumumab.
Shares Isatuximab, Daratumumab, Bortezomib, Lenalidomide.
Shares Newly diagnosed multiple myeloma, transplant-eligible, Daratumumab, Bortezomib, Lenalidomide.
Shares Newly diagnosed multiple myeloma, transplant-eligible, Daratumumab, Lenalidomide, Multiple myeloma.
Shares Daratumumab, Bortezomib, Lenalidomide, Multiple myeloma.
Shares MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Daratumumab, Lenalidomide, Multiple myeloma.
Shares CEPHEUS, IMROZ, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Isatuximab.
Shares PERSEUS, Newly diagnosed multiple myeloma, transplant-eligible, Daratumumab, Lenalidomide.