Janssen Pharmaceutical announced the submission of a Type II variation application to the European Medicines Agency (EMA) for DARZALEX® (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of patients newly diagnosed with multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).
“Today’s submission brings us one step closer to our goal of improving treatment outcomes for people newly diagnosed with multiple myeloma,” said José Antonio Burón Vidal, VP Medical Affairs, Europe, Middle East and Africa (EMEA), Janssen-Cilag Limited. “We are incredibly grateful to the patients and investigators who participated in the MAIA clinical trial programme and look forward to working closely with the regulatory authorities to secure approval of this new combination.”
The submission is supported by data from the Phase 3 MAIA (MMY3008) study, which were presented at the 60th Annual Meeting of the American Society of Hematology. The study showed that at a median follow-up of 28 months, daratumumab-Rd significantly reduced the risk of disease progression or death by 44 percent in patients with newly diagnosed multiple myeloma who are transplant ineligible compared to treatment with Rd alone (Hazard Ratio [HR] = 0.56; 95 percent confidence interval [CI]: 0.43-0.73; p<0.0001). The median progression-free survival (PFS) for daratumumab-Rd has not yet been reached, compared to 31.9 months for patients who received Rd alone. The addition of daratumumab resulted in deeper responses compared to Rd alone, including increased rates of complete response (CR) or better (48 percent vs. 25 percent) and improved rates of very good partial response (VGPR) or better (79 percent vs. 53 percent). Within the study, patient health, functional capacity, symptoms, psychosocial well-being, and life satisfaction were evaluated through measures to assess change in health-related quality of life by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Euro Quality of Life (EQ-5D-5L) Health State Profile Utility Score.
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The most common Grade 3/4 treatment-emergent adverse events (TEAEs) for daratumumab-Rd (≥10 percent) included neutropenia (50 percent), lymphopenia (15 percent), pneumonia (14 percent) and anaemia (12 percent). Infusion-related reactions (IRRs) occurred in 41 percent of patients receiving daratumumab-Rd, 3 percent of which were Grade 3/4. Incidence of invasive second primary malignancy was 3 percent in the daratumumab-Rd arm compared to 4 percent with Rd alone. TEAEs with an outcome of death were 7 percent in the daratumumab-Rd arm compared to 6 percent in the Rd arm. The safety profile of daratumumab was consistent with that of previous studies.
Daratumumab-Rd is being reviewed by the U.S. Food and Drug Administration (FDA) under the Real-Time Oncology Review (RTOR) pilot program.
In Europe, daratumumab is indicated:
- In combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant
- As monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy
- In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.