On January 27, 2026, the U.S. Food and Drug Administration (FDA) approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).
This approval expands frontline options for a population that represents a substantial proportion of newly diagnosed patients and historically has had fewer opportunities to achieve deep, durable responses.
Multiple Myeloma: Symptoms, Causes, Stages, Diagnosis and Treatment
Clinical Evidence: CEPHEUS Trial
The approval is based on CEPHEUS, an open-label, randomized, active-controlled Phase III trial enrolling patients with newly diagnosed multiple myeloma who were ASCT-ineligible or declined transplant as initial therapy.
Total patients: 395
Randomization:
- Darzalex Faspro + VRd (n=197)
- VRd alone (n=198)
Primary Efficacy Endpoints
- Minimal Residual Disease (MRD) Negativity
- Progression-Free Survival (PFS)
(assessed by an independent review committee using IMWG criteria)
Key Efficacy Results
MRD Negativity Rate
- Dara-VRd: 52.3%
- VRd alone: 34.8%
- p = 0.0005
Progression-Free Survival
- Hazard Ratio: 0.60
- 95% CI: 0.41–0.88
- p = 0.0078
These findings demonstrate both deeper responses and meaningful disease control, reinforcing MRD negativity as a surrogate marker increasingly linked to long-term outcomes in multiple myeloma.
Safety Profile
The safety profile of Darzalex Faspro-VRd was consistent with known risks of daratumumab-based therapy. The prescribing information includes warnings and precautions for:
- Hypersensitivity and administration-related reactions
- Infections
- Neutropenia and thrombocytopenia
- Embryo-fetal toxicity
- Interference with blood compatibility testing (RBC cross-matching)
- Cardiac toxicity in patients with light-chain (AL) amyloidosis
No new unexpected safety signals were identified.
Why This Approval Matters
- Sets a new frontline standard for transplant-ineligible patients with newly diagnosed multiple myeloma
- Confirms the value of quadruplet therapy beyond transplant-eligible populations
- Strengthens the role of MRD negativity as a clinically meaningful endpoint
- Offers a subcutaneous daratumumab formulation, reducing infusion burden and improving convenience
- Aligns real-world patient needs with modern, depth-of-response–driven treatment strategies
Bottom Line
With this FDA approval, Darzalex Faspro + VRd becomes a frontline cornerstone regimen for transplant-ineligible newly diagnosed multiple myeloma—bringing deeper remissions, longer disease control, and practical administration advantages to a population with high unmet need.