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In patients who were transplant-ineligible or deferred transplant, the daratumumab quadruplet raised deep-remission rates from about 39% to 61% and cut progression risk by 43%.
CEPHEUS randomised 395 patients with newly diagnosed multiple myeloma who were transplant-ineligible or for whom transplant was deferred to daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRd) or VRd. Unusually, the primary endpoint was the overall MRD-negativity rate at 10^-5 sensitivity, reflecting the FDA advisory committee's 2024 acceptance of MRD as an endpoint supporting accelerated approval. MRD-negativity was 60.9% versus 39.4%, complete response or better 81.2% versus 61.6%, and PFS favoured D-VRd (hazard ratio 0.57). Toxicity was in line with other daratumumab quadruplets.
CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.
Shares MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), CD38, Daratumumab, Bortezomib.
Shares CEPHEUS, IMROZ, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Daratumumab.
Shares MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, Newly diagnosed multiple myeloma, transplant-ineligible, Daratumumab, Lenalidomide.
Shares IMROZ, MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant, CD38, Multiple myeloma.
Shares MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), Daratumumab, Dormant cells and minimal residual disease, Lenalidomide.
Shares Daratumumab, Bortezomib, Lenalidomide, Johnson & Johnson.
Shares Daratumumab, Lenalidomide, Johnson & Johnson, MRD / molecular residual disease testing.
Shares MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), Daratumumab, Bortezomib, Lenalidomide.