Janssen-Cilag International NV’s European Commission (EC) approval extends the Darzalex (daratumumab) subcutaneous (SC) formulation for use in combination with bortezomib, lenalidomide, and dexamethasone. This combination is now an approved option for newly diagnosed multiple myeloma (NDMM) patients eligible for autologous stem cell transplants (ASCT). The quadruplet therapy offers a novel treatment approach that can significantly improve progression-free survival and treatment outcomes for these patients.
Evidence from the Perseus study
This approval stems from compelling data in the Phase 3 Perseus study, highlighting the superiority of daratumumab SC in the quadruplet regimen over existing therapies. Researchers evaluated the daratumumab-VRd regimen (daratumumab, bortezomib, lenalidomide, dexamethasone) as an induction and consolidation therapy, with daratumumab SC and lenalidomide (D-R) maintenance. This regimen was compared to the VRd regimen followed by lenalidomide (R) maintenance in newly diagnosed ASCT-eligible patients.
Key findings from PERSEUS, presented at the 2023 American Society of Hematology (ASH) Annual Meeting and published in The New England Journal of Medicine, were crucial for the approval. The study found a 58% reduction in disease progression or death for patients treated with the daratumumab-VRd regimen compared to VRd alone (HR, 0.42; 95% CI, 0.30-0.59; p<0.0001).
After a median 47.5-month follow-up, the daratumumab-VRd group demonstrated:
- Enhanced progression-free survival, a major advancement for newly diagnosed patients.
- An MRD-negativity rate of 75.2% versus 47.5% in the VRd group.
- Complete response rates of 87.9% for daratumumab-VRd, compared to 70.1% for VRd.
- 64.8% sustained MRD negativity for at least 12 months versus 29.7% in VRd.
These data reinforce the daratumumab SC-based regimen’s potential to provide durable responses, supporting long-term disease management and progression delay.
Expanding treatment horizons
“The approval of this SC-based quadruplet regimen offers a practice-changing option for patients,” said Dr. Paula Rodriguez-Otero of the Department of Hematology, Cancer Center Clínica Universidad de Navarra. “It can significantly enhance progression-free survival, complete response rates, and MRD-negativity status compared to the standard of care.”
This approval underscores daratumumab SC’s role as a foundational component in multiple myeloma treatment, particularly in frontline settings, giving oncologists a new tool to refine treatment strategies for superior outcomes.
Safety and side effects
The safety profile of the daratumumab-VRd regimen was consistent with known profiles for daratumumab SC and VRd. The most frequently reported hematologic adverse reactions included neutropenia, thrombocytopenia, and anemia. Non-hematologic side effects included peripheral neuropathy, fatigue, respiratory infections, COVID-19, and gastrointestinal symptoms like constipation and diarrhea. Despite a slightly higher frequency of some adverse reactions in the daratumumab-VRd group, the clinical benefits outweighed these risks, prompting the EC's approval.
A new milestone in myeloma treatment
Edmond Chan, Senior Director and EMEA Therapeutic Area Lead in Hematology at Johnson & Johnson, welcomed the approval as a transformative moment. “Integrating daratumumab SC into this regimen allows us to refine frontline therapy, setting a new benchmark for eligible patients from induction through to maintenance.”
With over half a million patients treated globally since its initial approval in 2016, daratumumab continues to evolve through combination regimens, marking significant strides toward managing—and one day potentially eliminating—multiple myeloma.
The approval grants patients and healthcare providers across the European Union a promising, effective treatment choice, representing a critical step in the pursuit of disease control and improved survival for patients facing this challenging blood cancer.
