FDA Approves Darzalex Faspro Quadruplet Regimen for Transplant-Eligible Multiple Myeloma
Key Insights
The FDA has approved Darzalex Faspro (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for newly diagnosed multiple myeloma (search) patients eligible for autologous stem cell transplant.
The approval was based on the Phase 3 PERSEUS study, which demonstrated a 60% reduction in the risk of disease progression or death with the D-VRd regimen compared to VRd alone.
Treatment with D-VRd resulted in significantly deeper responses, with minimal residual disease (MRD) negativity rates of 57.5% compared to 32.5% with VRd.
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 induction and consolidation treatment in patients with newly diagnosed multiple myeloma (search) (NDMM) who are eligible for autologous stem cell transplant (ASCT). This approval marks a significant advancement in the treatment landscape, offering patients a new first-line option that may substantially improve outcomes.
The approval is based on data from the Phase 3 PERSEUS study, which evaluated Darzalex Faspro in a regimen that included D-VRd induction and consolidation therapy compared to bortezomib, lenalidomide, and dexamethasone (VRd) during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included Darzalex Faspro in combination with lenalidomide or lenalidomide alone.
Significant Improvement in Progression-Free Survival
The PERSEUS study demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), with D-VRd reducing the risk of disease progression or death by 60 percent compared to VRd (HR [95% CI]: 0.40 [0.29, 0.57]; p-value < 0.0001). This indicates a substantial benefit in delaying disease progression for patients receiving the Darzalex Faspro-based quadruplet therapy.
Deeper Responses with D-VRd Regimen
Treatment with D-VRd induction and consolidation resulted in deeper responses at the end of consolidation compared to VRd. Minimal residual disease (MRD) negativity rates were 57.5 percent in the D-VRd arm versus 32.5 percent in the VRd arm. Furthermore, MRD-negativity rates in patients with complete response (CR) or better were 76.6 percent versus 58.5 percent, respectively.
Safety and Tolerability
The overall safety profile of D-VRd was consistent with the known safety profiles for Darzalex Faspro and VRd. The most common adverse reactions (≥20%) in patients with multiple myeloma (search) who received D-VRd are peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
About the PERSEUS Study
The PERSEUS study is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia.
Multiple Myeloma Context
Multiple myeloma (search) is a blood cancer that affects plasma cells in the bone marrow. It is the second most common blood cancer worldwide and remains an incurable disease. In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease. People with multiple myeloma have a 5-year survival rate of 59.8 percent.
Darzalex Faspro: A CD38-Directed Antibody
Darzalex Faspro (daratumumab and hyaluronidase-fihj) is the only subcutaneous CD38 (search)-directed antibody approved to treat patients with multiple myeloma (search). This latest approval expands its use to nine indications in multiple myeloma, including four frontline treatments for newly diagnosed patients who are transplant eligible or ineligible.