CEPHEUS Outcomes Support Daratumumab Plus VRd as SOC in Multiple Myeloma

Saad Z. Usmani, MD, MBA, FACP, myeloma specialist and cellular therapist at Memorial Sloan Kettering Cancer Center, discussed the results of the CEPHEUS trial (NCT03652064) and further elaborated on the specific combinations of medications administered among the patients.

Usmani is presenting at the 21st annual International Myeloma Society conference taking place in Rio de Janeiro, Brazil, from September 25 to 27. Usmani will join various leading experts to discuss the basic, preclinical, and clinical aspects of myeloma.

This transcript was lightly edited for clarity.

Transcript

How will the results of the CEPHEUS study be used to inform the treatment of patients with newly diagnosed multiple myeloma?

Based on the CEPHEUS clinical trial, the transplant-ineligible or transplant-deferred patients who are fit or intermediate fit, may be able to get these quadruplet regimens in the frontline setting. This would help get them into deeper responses that translate into progression-free survival benefit. I think the results help inform standard-of-care practice and the fact that we'd be able to utilize the anti-CD38 monoclonal antibody–based quadruplets for these patients, as well.

How does the CEPHEUS study compare with other clinical trials that have investigated the use of daratumumab for patients with multiple myeloma?

The CEPHEUS trial builds on the previous positive results that were seen with daratumumab along with lenalidomide dexamethasone in the MAIA clinical trial [NCT02252172], setting a new benchmark for treating transplant-ineligible patients, with a median overall survival of 7 and a half years.

Here, we are adding a quadruplet regimen for patients, but perhaps who are more fit or relatively younger than the MAIA patient population, so they are able to get the 4-drug induction therapy and then the 2-drug maintenance treatment subsequently. This really builds on that MAIA clinical trial benchmark. I feel that the depth of response and PFS benefit that we're observing, looking at the curves, appears to be better than what we have observed with MAIA. This clinical trial will help make the case for quadruplet induction regimens for a significant number of transplant-ineligible or deferred patients.

Can you elaborate on the specific combinations of medications used in the trial, and how they were chosen?

VRd is considered a standard-of-care therapy for transplant-ineligible patients, as is DRd. VRd became the standard-of-care treatment for patients with myeloma based on the SWOG S0777 trial [NCT00644228] and that clinical trial was essentially utilized to inform the standard-of-care arm for the CEPHEUS study. Daratumumab has been combined with VRd in other clinical trials, in the GRIFFIN study [NCT02874742], in the PERSEUS study [NCT03710603], and it was examined for newly diagnosed patients in the transplant-ineligible or transplant-deferred space as part of the CEPHEUS study.