FDA Approves Darzalex Faspro-VRd For Newly Diagnosed, Transplant Ineligible Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has approved the use of Darzalex Faspro (daratumumab and hyaluronidase-fihj) in combination with Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone (VRd) for the treatment of adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).

The agency announced the approval on its website on Tuesday, Feb. 27.

The effectiveness of the treatment combination was evaluated in the CEPHEUS open-label, randomized, active-controlled trial in patients with newly diagnosed multiple myeloma who were ineligible for ASCT or refused ASCT as initial therapy. The effectiveness of Darzalex Faspro-VRd has not been established in patients who refused ASCT as initial therapy, the agency noted in its announcement of the approval.

In the trial, 395 patients were randomized: 197 to the Darzalex Faspro-VRd arm and 198 to the VRd arm. The major efficacy outcome measures of the trial were overall minimal residual disease (MRD) negativity rate and progression-free survival (PFS) by independent review committee (IRC) based on International Myeloma Working Group (IMWG) response criteria. The MRD negativity rate was 52.3% in the Darzalex Faspro-VRd arm and 34.8% in the VRd arm. The PFS hazard ratio was 0.60.

The agency advised that the prescribing information for the treatment combination includes warnings and precautions for hypersensitivity and other administration reactions, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity interference with cross-matching and red blood cell antibody screening, and cardiac toxicity in patients with light chain (AL) amyloidosis.

During a CURE Educated Patient® Summit in 2025, Dr. Cesar Rodriguez —an associate professor of medicine (hematology and medical oncology) at the Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute and the Center of Excellence for Multiple Myeloma, and Clinical Director of Multiple Myeloma at The Mount Sinai Hospital in New York City — discussed the findings of the CEPHEUS trial.

“We see here that by adding this fourth agent to three agents, there really is an added benefit in terms of the depth of the response and the control of the disease,” Rodriguez said during the summit. “And one would say, ‘OK, well, why are we doing this in somebody who's frail or who's transplant ineligible?’ It's a very good question, and we need to figure out, ‘OK, what is our goal for the treatment?’ Is our goal the treatment to achieve a remission and a durable remission, or is the goal of our treatment to just maintain the disease and to keep it from growth? If we really want to try to knock off the disease from the patient and we want to try to get the best control possible, then a combination of four drugs is possible, as you can see by this study.”

“These data support the use of [Darzalex] in combination with VRd as a normal standard of care in patients with newly diagnosed multiple myeloma who are transplant ineligible or when transplant is deferred,” Dr. Sonja Zweegman from the Department of Hematology at Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Netherlands, said during a presentation of the data from the CEPHEUS trial at the 2024 ASH Annual Meeting.

This regulatory announcement marks the latest approval by the FDA for the use of Darzalex Faspro, which was previously approved by the agency in late 2025 for the treatment of adults with high-risk smoldering multiple myeloma.

References

1. “FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma,” FDA; https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-newly
2. “Quadruplet Regimen Preferable to Triplets in Multiple Myeloma,” CURE; https://www.curetoday.com/view/quadruplet-regimen-preferable-to-triplets-in-multiple-myeloma
3. “Darzalex Regimen May Improve MRD Responses in Multiple Myeloma,” CURE; https://www.curetoday.com/view/darzalex-regimen-may-improve-mrd-responses-in-multiple-myeloma
4. “FDA Approves Darzalex Faspro in High-Risk Smoldering Multiple Myeloma,” CURE; https://www.curetoday.com/view/fda-approves-darzalex-faspro-in-high-risk-smoldering-multiple-myeloma

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