{"entity":{"id":"cd38-plus-triplet","kind":"pairing","name":"CD38 antibody added to PI-IMiD-dex (quadruplet induction)","aka":[],"tldr":"Adding a CD38 antibody to the standard three-drug induction roughly halves progression risk in newly diagnosed myeloma.","summary":"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.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03710603: PERSEUS","url":"https://clinicaltrials.gov/study/NCT03710603"},{"label":"ClinicalTrials.gov NCT03652064: CEPHEUS","url":"https://clinicaltrials.gov/study/NCT03652064"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["daratumumab","isatuximab","bortezomib","lenalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["perseus","cepheus","imroz"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"daratumumab","b":"lenalidomide","rationale":"Non-overlapping mechanisms: proteasome stress, cereblon-mediated degradation, and Fc-mediated plasma-cell killing with immunomodulation.","evidence":"Four positive phase 3 trials; OS benefit in MAIA.","pairingType":"combination"},"route":"/pairings/cd38-plus-triplet/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-transplant-eligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-eligible","route":"/cancers/myeloma-transplant-eligible/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"isatuximab","kind":"drug","name":"Isatuximab","route":"/drugs/isatuximab/"},{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"}],"trial":[{"id":"cepheus","kind":"trial","name":"CEPHEUS","route":"/trials/cepheus/"},{"id":"imroz","kind":"trial","name":"IMROZ","route":"/trials/imroz/"},{"id":"perseus","kind":"trial","name":"PERSEUS","route":"/trials/perseus/"}],"paper":[{"id":"paper-maia-daratumumab-rd-nejm-2019","kind":"paper","name":"MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant","route":"/key-papers/paper-maia-daratumumab-rd-nejm-2019/"},{"id":"paper-perseus-dara-vrd-transplant-nejm-2024","kind":"paper","name":"PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma","route":"/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/"}]}}