Background and Findings of the CEPHEUS Trial in Multiple Myeloma

Saad Z. Usmani, MD, MBA, FACP, FASCO, chief of the myeloma service at Memorial Sloan Kettering Cancer Center, discusses the phase 3 CEPHEUS trial (NCT03652064) of daratumumab (Darzalex) with bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma for whom hematopoietic stem cell transplant is not planned as initial therapy.

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0:09 | CEPHEUS is a phase 3 clinical trial comparing daratumumab subcutaneously along with VRd as induction, compared [with] VRd in patients with newly diagnosed multiple myeloma who are either transplant eligible or have deferred stem cell transplant, and the primary end point of this trial was achieving MRD negativity

0:37 | The study enrolled a total of 395 patients in 1:1 randomization. The median age of the patients was 70 years and 55 or more percent were 70 years or older. The patients primarily made up intermediate, fit, transplant ineligible, or transplant deferred patients, and the transplant deferred patients made up about 27% of the population. In terms of high-risk features, the ISS stage III was seen in 28% of the patients, and high-risk cytogenetics in about 13% of the patients. So, the treatment arms were fairly well-balanced.

1:30 | So, the study met its primary end point in terms of overall MRD-negativity rate at 10-5, showing about 61% compared [with] 39% on the standard-of-care arm. So, there is an overall increase of approximately 20% in MRD-negativity in [complete response] or better patients, and then sustained MRD negativity was also superior at the 12-month mark, 48.7% vs 26.3%. And at a median follow-up of 58.7 months, the median PFS has not been reached in the [daratumumab plus] VRd arm, whereas in the VRd arm, it is 52.6 months. At month 54, the PFS rates [are] 68.1% vs 49.5% and the hazard ratio is .57, and it is statistically significant. These are very exciting results and they further cement the place of quadruplet induction treatment for multiple myeloma in the frontline setting.