# CD38 antibody added to PI-IMiD-dex (quadruplet induction)

Source: https://onco.cc/pairings/cd38-plus-triplet/  
OnCo record `cd38-plus-triplet` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Daratumumab + Lenalidomide
- Type: combination
- 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.

## Sources

- ClinicalTrials.gov NCT03710603: PERSEUS: https://clinicaltrials.gov/study/NCT03710603
- ClinicalTrials.gov NCT03652064: CEPHEUS: https://clinicaltrials.gov/study/NCT03652064

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Newly diagnosed multiple myeloma, transplant-eligible](https://onco.cc/cancers/myeloma-transplant-eligible/)
- drugs: [Bortezomib](https://onco.cc/drugs/bortezomib/), [Daratumumab](https://onco.cc/drugs/daratumumab/), [Isatuximab](https://onco.cc/drugs/isatuximab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/)
- trials: [CEPHEUS](https://onco.cc/trials/cepheus/), [IMROZ](https://onco.cc/trials/imroz/), [PERSEUS](https://onco.cc/trials/perseus/)
- key papers: [MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant](https://onco.cc/key-papers/paper-maia-daratumumab-rd-nejm-2019/), [PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma](https://onco.cc/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/)

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