The FDA has approved DARZALEX FASPRO plus VRd (D-VRd) for transplant-ineligible adults with newly diagnosed multiple myeloma, supported by Phase 3 CEPHEUS data showing deeper responses and higher MRD-negativity rates.
Written By: Pharmacally Medical News Desk
Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT). The approval expands the use of DARZALEX FASPRO-based quadruplet therapy to a broader frontline patient population and makes D-VRd the only anti-CD38 antibody-based regimen approved across newly diagnosed patients regardless of transplant eligibility.
June Lanoue, U.S. President of Hematology at Johnson & Johnson Innovative Medicine, said the FDA decision represents the twelfth overall indication for DARZALEX FASPRO and the fifth in newly diagnosed multiple myeloma, reinforcing its role as a foundational therapy. She added that CEPHEUS supports D-VRd as a frontline standard of care, allowing patients to receive the quadruplet regimen at diagnosis as part of the company’s long-term goal of achieving a functional cure.
Clinical Data
The Phase 3 CEPHEUS trial (NCT03652064) is a multicentre, randomized, open-label Phase 3 trial enrolling 395 patients across 13 countries; demonstrated that DARZALEX FASPRO plus VRd (D-VRd) provided significant improvements across multiple endpoints compared with VRd alone in transplant-ineligible newly diagnosed multiple myeloma patients. At a median follow-up of 22 months, the MRD-negativity rate was 52.3% with D-VRd vs 34.8% with VRd. At a median follow-up of 39 months, sustained MRD-negativity for ≥12 months was 42.6% vs 25.3%, respectively, and D-VRd reduced the risk of progression or death by 40%. With nearly 5 years of follow-up (59 months), the complete response or better rate was 81.2% with D-VRd vs 61.6% with VRd, while overall survival data were not yet mature.
The safety profile of D-VRd was consistent with the known effects of DARZALEX FASPRO and VRd, with the most common adverse events including upper respiratory tract infections, sensory neuropathy, fatigue, diarrhea, musculoskeletal pain, rash, edema, pneumonia, renal impairment, and COVID-19, and no unexpected safety concerns were reported.
Saad Z. Usmani, MD, Chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center and principal investigator of CEPHEUS, said D-VRd delivered deeper and more durable responses, significantly lowered the risk of progression or death, and nearly doubled sustained MRD-negativity rates compared with VRd in transplant-ineligible patients. He noted that MRD-negativity is an important predictor of long-term outcomes and that D-VRd is the only FDA-approved quadruplet regimen supported by a study using MRD-negativity as the primary endpoint.
About DARZALEX FASPRO® and DARZALEX
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) was first approved by the U.S. FDA in May 2020 and has since become a key therapy in multiple myeloma. It remains the only subcutaneous CD38-directed antibody approved for the treatment of multiple myeloma and is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) using Halozyme’s ENHANZE® drug delivery technology.
DARZALEX® (intravenous daratumumab) received its initial FDA approval in November 2015 and was the first CD38-directed antibody authorized for multiple myeloma. It is currently approved in eight indications, including three in the frontline setting for newly diagnosed transplant-eligible and transplant-ineligible patients.
DARZALEX-based regimens have now been used to treat more than 720,000 patients worldwide, underscoring their global impact in multiple myeloma care.
Daratumumab was licensed through a worldwide agreement signed in August 2012 between Janssen Biotech, Inc. and Genmab A/S, granting Janssen exclusive rights to develop, manufacture, and commercialize the therapy.
Reference
DARZALEX FASPRO®–based quadruplet regimen approved in the U.S. for newly diagnosed patients with multiple myeloma who are transplant ineligible, 27 January 2026, DARZALEX FASPRO®-based quadruplet regimen approved in the U.S. for newly diagnosed patients with multiple myeloma who are transplant ineligible
A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy, ClinicalTrials.gov ID NCT03652064, https://clinicaltrials.gov/study/NCT03652064
Usmani SZ 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 Apr;31(4):1195-1202. doi: 10.1038/s41591-024-03485-7. Epub 2025 Feb 5. Erratum in: Nat Med. 2025 Apr;31(4):1366. PMID: 39910273; PMCID: PMC12003169. https://doi.org/10.1038/s41591-024-03485-7