FDA Approves Daratumumab Regimen for Transplant-Ineligible Myeloma

The Food and Drug Administration approved daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (Rd) for the treatment of patients with newly diagnosed myeloma who are not eligible for autologous stem cell transplant (ASCT), according to Janssen, the manufacturer of the drug.

The approval is based off the phase III MAIA trial, that showed that daratumumab plus Rd reduced the risk of disease progression or death by 44% compared to patients who received Rd alone.

"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, MD, FACP, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, and a lead investigator of the MAIA study, in a statement.

Median progression-free survival (PFS) in the MAIA study was not yet reached in the daratumumab arm, and was 31.9 months in patients who received Rd alone. Patients randomized to daratumumab had deeper responses compared to the Rd arm, as well as higher complete response (CR) rates (48% versus 25%, respectively). There was also a higher very good partial response rate or better (79% versus 53%, respectively), and overall response rate (93% versus 81%, respectively).

Of note, the daratumumab arm had more than a 3 times higher rate of minimal residual disease (MRD) negativity compared to the Rd arm (24% versus 7%).

"For patients with multiple myeloma, optimizing response to frontline treatment is critical," said Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation. "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."

The most frequent adverse events (AE) that occurred in at least 20% of patients on the daratumumab arm included: 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% greater incidence in the daratumumab-Rd arm compared to the Rd arm were pneumonia (15% vs. 8%), bronchitis (4% vs. 2%) and dehydration (2% vs. less than 1%), respectively. Treatment-emergent grade 3/4 hematology laboratory abnormalities (more than 20%) were neutropenia (56%), lymphopenia (52%) and leukopenia (35%). The safety profile of daratumumab was consistent with that of previous studies.

"Today's 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, in a statement.

"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."