The Janssen Pharmaceutical Companies of Johnson & Johnson announced the U.S. Food and Drug Administration (FDA) approval of DARZALEX® (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).
The approval is based on results from the Phase 3 MAIA (MMY3008) clinical study, which showed that DARZALEX-Rd significantly reduced the risk of disease progression or death by 44 percent compared to treatment with Rd alone. The application received approval through the U.S. FDA’s Real-Time Oncology Review (RTOR) pilot program.
“Multiple myeloma can become more difficult to treat after relapse, so it is important that patients receive an efficacious upfront therapy with a goal of extending their first remission period,”
said Saad Usmani, M.D., FACP, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, and a lead investigator of the MAIA study.
“This regimen offers an important frontline treatment option for this patient population, and it has been submitted to the NCCN Multiple Myeloma Panel for review and consideration for potential inclusion in the NCCN Clinical Practice Guidelines.”
Data from the Phase 3 MAIA study were recently published in The New England Journal of Medicine and previously presented at the 2018 American Society of Hematology (ASH) Annual Meeting. At a median follow-up of 28 months, results showed DARZALEX in combination with 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 DARZALEX-Rd has not yet been reached, compared to 31.9 months for patients who received Rd alone.1 The addition of DARZALEX resulted in deeper responses compared to Rd alone, including increased rates of complete response (CR) or better (48 percent vs. 25 percent), very good partial response (VGPR) or better (79 percent vs. 53 percent) and overall response (93 percent vs. 81 percent). DARZALEX-Rd induced a >3-fold higher rate of minimal residual disease (MRD) negativity compared to Rd alone (24 percent vs. 7 percent).
“For patients with multiple myeloma, optimizing response to frontline treatment is critical. This latest indication for DARZALEX is a promising development for the myeloma community, and we are grateful to Janssen, our long-standing partner in myeloma research, as well as the patients with myeloma and healthcare providers involved in this study,”
said Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation.
“Approval of DARZALEX underscores the significant clinical benefit of this CD38 monoclonal antibody and our efforts to advance treatment paradigms to change the course of the disease,”
said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC.
“Importantly, this milestone also highlights the efficiency of the FDA’s Real-Time Oncology Review process, ensuring that proven treatment regimens, such as DARZALEX plus lenalidomide and dexamethasone, are made available to patients as soon as possible.”
The most frequent (≥20 percent) adverse reactions were infusion reactions, diarrhea, constipation, nausea, peripheral edema, fatigue, back pain, asthenia, pyrexia, upper respiratory tract infection, bronchitis, pneumonia, decreased appetite, muscle spasms, peripheral sensory neuropathy, dyspnea and cough. Serious adverse reactions with a 2 percent greater incidence in the DARALEX-Rd arm compared to the Rd arm were pneumonia (15 percent vs. 8 percent), bronchitis (4 percent vs. 2 percent) and dehydration (2 percent vs. <1 percent), respectively. Treatment-emergent Grade 3/4 hematology laboratory abnormalities (≥20 percent) were neutropenia (56 percent), lymphopenia (52 percent) and leukopenia (35 percent). The safety profile of DARZALEX was consistent with that of previous studies.