The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending approval of a Type II variation for Janssen's Darzalex (daratumumab) subcutaneous (SC) formulation. The recommendation supports the use of daratumumab SC in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for treating adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem-cell transplant (ASCT). This decision follows the recent FDA approval of the same regimen in the United States. The SC formulation was previously approved by the European Commission in June 2020.
This recommendation is based on data from the Phase 3 PERSEUS study (NCT03710603), which evaluated D-VRd induction and consolidation therapy, along with daratumumab and lenalidomide (D-R) maintenance therapy, compared to VRd induction and consolidation, and R maintenance, in transplant-eligible patients with newly diagnosed multiple myeloma. The study's data were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
Key Findings from the PERSEUS Study
The PERSEUS study demonstrated a significant improvement in progression-free survival (PFS) with the daratumumab-based quadruplet regimen. Specifically, the findings showed a 60% reduction in the risk of disease progression or death with the daratumumab SC quadruplet regimen compared to the current standard-of-care triplet regimen. At a median follow-up of 47.5 months, the estimated 48-month PFS rate was 84.3% with D-VRd compared to 67.7% with VRd alone (HR, 0.42; 95% CI, 0.30-0.59; P < .001).
Deep and durable minimal residual disease (MRD) negativity was also more frequently achieved with D-VRd. The percentage of patients with MRD-negative status (sensitivity threshold of 10-5) was 75.2% in the D-VRd arm versus 47.5% in the VRd arm (OR, 3.40; 95% CI, 2.47-4.69; P < .0001). Furthermore, a higher proportion of patients in the D-VRd arm converted to MRD-negative status during the maintenance phase compared to the VRd arm (60.2% vs 40.5% for MRD negativity at 10-5, P = .0049; 56.7% vs 25.2% for MRD negativity at 10-6, P < .0001).
Daratumumab's Role in Multiple Myeloma Treatment
Daratumumab, a CD38-directed antibody, has become a foundational therapy for multiple myeloma since its initial European approval in 2016. It is currently approved in eight indications for multiple myeloma, four of which are in the frontline setting. Daratumumab binds to the CD38 protein, which is highly expressed on multiple myeloma cells, inhibiting tumor cell growth and inducing myeloma cell death.
According to Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine, "Optimising frontline therapy is crucial in disease control and improving long-term outcomes for patients with newly diagnosed multiple myeloma. By incorporating daratumumab SC into this novel quadruplet regimen, we aim to establish a new standard of care for eligible patients, enhancing progression-free survival and transforming the treatment landscape."
Multiple Myeloma: An Incurable Blood Cancer
Multiple myeloma is an incurable blood cancer affecting plasma cells in the bone marrow. In the European Union, an estimated 35,000+ individuals were diagnosed with multiple myeloma in 2022, and over 22,700 patients died. While some patients are asymptomatic initially, others experience bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections, or kidney damage.
