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CEPHEUS

Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial

Phase 3N = 395NCT03652064

Population
Newly diagnosed multiple myeloma, transplant-ineligible or transplant-deferred.
Design
Phase 3 trial: 395 patients with transplant-ineligible newly diagnosed myeloma, or for whom transplant was not planned as initial therapy, were randomly assigned to eight cycles of subcutaneous daratumumab plus VRd or VRd, followed by daratumumab plus Rd or Rd until progression. The primary end point was the overall MRD-negativity rate at 10^-5 by next-generation sequencing. Progression-free survival was a major secondary end point.
Primary endpoint
MRD
Arms
  • Daratumumab + VRd (experimental): Subcutaneous daratumumab with bortezomib, lenalidomide and dexamethasone for eight cycles, then daratumumab with lenalidomide and dexamethasone
  • VRd (control): Bortezomib, lenalidomide and dexamethasone for eight cycles, then lenalidomide and dexamethasone
People
Usmani SZ
Δ MRD+21.5 pointsΔ ≥CR rate+19.6 pointsΔ MRD+22.4 pointsPFSHR 0.57 (95% CI 0.41–0.79)
Show the numbers
Results reported for CEPHEUS
EndpointAnalysisDaratumumab + VRdVRdEffect
MRDTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 202560.9%39.4%P<0.0001Overall MRD negativity at a threshold of 10^-5 by next-generation sequencing. Odds ratio 2.37 (95% CI 1.58 to 3.55).
≥CR rateTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 202581.2%61.6%P<0.0001
MRDTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 202548.7%26.3%P<0.0001Sustained MRD negativity for at least 12 months.
PFSTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 2025——HR 0.57 (95% CI 0.41–0.79)P=0.0005Major secondary end point.
Results reported for CEPHEUS
EndpointAnalysisDaratumumab + VRdVRdEffect
MRDTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 202560.9%39.4%P<0.0001Overall MRD negativity at a threshold of 10^-5 by next-generation sequencing. Odds ratio 2.37 (95% CI 1.58 to 3.55).
≥CR rateTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 202581.2%61.6%P<0.0001
MRDTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 202548.7%26.3%P<0.0001Sustained MRD negativity for at least 12 months.
PFSTransplant-ineligible or transplant-deferred patients (395)primarymedian follow-up 58.7 monthsUsmani 2025——HR 0.57 (95% CI 0.41–0.79)P=0.0005Major secondary end point.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.570.41–0.79
Primary publication: Usmani SZ, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025;31(4):1195-1202. PubMedDOI

Appears in

Sources

  1. Usmani SZ, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025;31(4):1195-1202.

    PubMedDOI