Key Takeaways
- Daratumumab and hyaluronidase-fihj in combination with bortezomib, and dexamethasone (D-VRd) now available for the treatment of adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant
- Clinicians should balance the higher depth of response and longer progression-free survival achievable with quadruplet D-VRd therapy against the improved tolerability offered by triplet daratumumab-lenalidomide-dexamethasone therapy when considering which regimen to choose
- The decision for treatment will be based on the individual patient’s overall treatment goals and their perceived ability to tolerate the addition of bortezomib
The FDA approved the quadruplet regimen of daratumumab and hyaluronidase-fihj in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for the treatment of adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.1
The recommended dose of daratumumab and hyaluronidase-fihj is 1800 mg/30,000 units administered subcutaneously.
The FDA granted approval based on the efficacy demonstrated in the CEPHEUS trial, which randomized 395 patients: 197 to the D-VRd arm and 198 to the bortezomib- lenalidomide-dexamethasone arm. The trial showed significant improvements in minimal residual disease negativity rates (52.3% vs 34.8%; P=.0005) and progression-free survival (PFS), with a hazard ratio of 0.60 (95% CI, 0.41-0.88; P=.0078).
“With D-VRd, physicians have an increased ability to tailor frontline daratumumab-based combination therapy to the patient’s age, frailty and other patient-related and disease-related risk factors,” the study authors wrote. “It will be important to balance the higher depth of response and longer PFS achievable with quadruplet D-VRd therapy with the improved tolerability offered by triplet [daratumumab-lenalidomide-dexamethasone] therapy, with the ultimate decision probably based on the individual patient’s overall treatment goals and perceived ability to tolerate the addition of bortezomib.”2
When considering D-VRd for patients, FDA warnings and precautions include:
- Hypersensitivity and other administration reactions
- Infections
- Neutropenia
- Thrombocytopenia
- Embryo-fetal toxicity
- Cardiac toxicity in patients with light chain amyloidosis
References
- U.S. Food and Drug Administration. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. Published January 27, 2026. Accessed April 10, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-newly
- Usmani SZ, Facon T, Hungria V, 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;31:1195-1202. doi:10.1038/s41591-024-03485-7