FDA Approves Darzalex-Revlimid-dexamethasone Combo to Treat Newly Diagnosed Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has approved Janssen‘s Darzalex (daratumumab), used in combination with Revlimid (lenalidomide) and dexamethasone, to treat patients newly diagnosed with multiple myeloma who are ineligible to receive an autologous stem cell transplant (ASCT).

Darzalex is an antibody designed to recognize and block the activity of CD38, a protein found on the surface of multiple myeloma cells, to prevent growth of cancer cells and eliminate them. It was originally developed by Genmab, and then licensed to Janssen in August 2012.

This is the sixth Darzalex treatment regimen that the FDA has approved for the treatment of patients with multiple myeloma, and the second for those who have just been diagnosed.

Darzalex’s application was approved through the Real-Time Oncology Review (RTOR) pilot program and was granted priority review by the FDA. The main purpose of the FDA’s RTOR program is to improve the review process of safe and effective medications, so that they can become available to patients as soon as possible.

“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,” Craig Tendler, MD, vice president of clinical development and global medical affairs, oncology, Janssen Research & Development, said in a press release.

“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,” he added.

The approval was based on findings from the multicenter, randomized, open-label MAIA Phase 3 trial (NCT02252172).

The study was designed to assess whether Darzalex (16 mg/kg) in combination with the immunomodulatory agent Revlimid and the corticosteroid dexamethasone — DRd combo — could improve the clinical outcomes of 737 patients who had been newly diagnosed with multiple myeloma and were not eligible for high-dose chemotherapy and ASCT.

Previous findings from MAIA, recently published in the New England Journal of Medicine and presented during the 2018 ASH Meeting, showed that:

• At a follow-up of 28 months, the DRd combo reduced the risk of disease progression or death by 44%, compared with the Revlimid-and-dexamethasone (Rd) standard treatment regimen.
• The DRd combo prolonged patients’ median progression-free survival (PFS or the time patients lived without their disease worsening), which has not been reached yet in the study, compared with the Rd standard treatment regimen (PFS of 31.9 months).
• The DRd combo increased the percentage of patients showing an overall response to therapy, compared with the standard treatment regimen (93% versus 81%). The DRd combo increased the percentage of patients achieving a complete response (48% versus 25%), or a very good partial response (79% versus 53%), compared with the Rd combo.
• The triple combination increased the percentage of patients achieving a state of minimal residual disease (MRD) negativity (less than one malignant cancer cell found among 10,000 white blood cells) by more than three times compared with the standard therapy regimen (24% versus 7%);
• The median time to response was identical in patients treated with both therapy regimens (1.05 months in both groups).
• The median response duration has not been reached yet for patients in the DRd group, and was 34.7 months among patients in the Rd group;
• The most common adverse events occurring in the trial included infusion reactions, diarrhea, constipation, nausea, peripheral edema, fatigue, back pain, asthenia, weakness, fever, upper respiratory tract infection, bronchitis, pneumonia, decreased appetite, muscle spasms, peripheral sensory neuropathy, shortness of breath, and cough.
• Some serious adverse events were more frequent among patients in the DRd combo than in the Rd treatment, such as pneumonia (15% versus 8%), bronchitis (4% versus 2%) and dehydration (2% versus less than 1%).

The full prescribing information for the DRd combo, including recommended doses, schedules and possible side effects, can be found here.

“For patients with multiple myeloma, optimizing response to frontline treatment is critical,” explained 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,” he said.