FDA approved Darzalex Faspro (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

The agency’s approval makes the daratumumab-based quadruplet regimen available for newly diagnosed patients regardless of transplant eligibility and establishes it as the only anti-CD38 antibody-based regimen approved across this patient population.¹

Darzalex Faspro is a subcutaneous formulation of daratumumab and has received approved across several indications for multiple myeloma, including an approval for adults with High-Risk Smoldering Multiple Myeloma back in November last year.

The most recent FDA approval expands its use in newly diagnosed disease based on clinical evidence demonstrating deeper and more durable responses when added to standard therapy in patients not undergoing transplant and builds on the agency’s advisory committee vote from May 2025, supporting the treatment for high-risk smoldering multiple myeloma.

What was FDA’s approval based on?

The decision is based on results collected from the Phase III Cepheus study evaluating the efficacy and safety of the Darzalex Faspro -based combination compared with bortezomib, lenalidomide, and dexamethasone alone in patients with newly diagnosed multiple myeloma who were ineligible for or deferred autologous stem cell transplant as initial therapy.¹

“D-VRd increased the depth and durability of responses, significantly reduced the risk of disease progression or death, and nearly doubled the rate of sustained minimal residual disease (MRD)-negativity compared to VRd in patients ineligible for ASCT, solidifying this regimen as a potential standard of care for newly diagnosed patients with multiple myeloma,” said Saad Z. Usmani, M.D., chief, myeloma service at Memorial Sloan Kettering Cancer Center and Cepheus principal investigator. “MRD-negativity is a potential predictor of prolonged progression-free and overall survival and D-VRd is now the only quadruplet regimen approved by the FDA based on a study with MRD-negativity as a primary endpoint.”

Cepheus was a multicenter, randomized, open-label, Phase III study enrolling 395 patients across 13 countries in North America, South America, and Europe. The trial compared Darzalex Faspro plus bortezomib, lenalidomide, and dexamethasone with the three-drug regimen alone. The primary endpoint was overall minimal residual disease negativity at a sensitivity threshold of 10⁻⁵, with key secondary endpoints including complete response or better, progression-free survival, sustained minimal residual disease negativity, overall response rate, overall survival and safety.¹

At a median follow-up of 22 months, the overall minimal residual disease negativity rate was 52.3% in patients treated with the daratumumab-based regimen compared with 34.8% in the control group. At 39 months, the proportion of patients achieving sustained minimal residual disease negativity for at least 12 months was 42.6% compared with 25.3% and treatment with the quadruplet reducing the risk of disease progression or death by 40%.¹ 

The safety profile observed in Cepheus was consistent with the known safety profiles of Darzalex Faspro and the backbone regimen. The most common adverse events reported in patients receiving the daratumumab-based combination included the following:

• Upper respiratory tract infection
• Sensory neuropathy
• Musculoskeletal pain
• Diarrhea, fatigue
• Edema
• Rash
• Motor dysfunction
• Covid-19
• Constipation
• Sleep disorder
• Cough pneumonia
• Renal impairment
• Dizziness, nausea
• Urinary tract infection
• Pyrexia
• Abdominal pain
• Dyspnea
• Decreased appetite
• Bruising

“This approval marks the twelfth indication for Darzalex Faspro overall and fifth in newly diagnosed multiple myeloma, underscoring its role as foundational therapy for both newly diagnosed and relapsed/refractory patients,” said June Lanoue, U.S. president, hematology, Johnson & Johnson Innovative Medicine. “Cepheus demonstrated the efficacy of a Darzalex Faspro-based quadruplet as a frontline standard of care. With this approval, patients can receive D-VRd when they are first diagnosed with multiple myeloma, an important milestone as we work to one day deliver a functional cure.”

Sources

1. Darzalex Faspro-based Quadruplet Regimen Approved in the U.S. for Newly dDagnosed Patients with Multiple Myeloma Who are transplant Ineligible Johnson & Johnson Janurary 27, 2026 https://www.jnj.com/media-center/press-releases/darzalex-faspro-based-quadruplet-regimen-approved-in-the-u-s-for-newly-diagnosed-patients-with-multiple-myeloma-who-are-transplant-ineligible