FDA Approves Daratumumab as Combination Multiple Myeloma Drug

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex) as a combination therapy for patients with multiple myeloma ineligible for autologous stem cell transplant (ASCT).

The indication, which approves the Janssen therapy in combination with lenalidomide and dexamethasone (Rd), was approved through the FDA’s Real-Time Oncology Review (RTOR) pilot program—expediting the therapy’s availability to at-need patients.

Daratumumab’s approval was based on the results of the phase 3 MAIA (MMY3008) clinical trial, in which the therapy plus Rd significantly reduced multiple myeloma progression or death by 44% compared to lone Rd treatment (HR .56; 95% CI: .43 - .73; P < .0001).

The findings, presented at the American Society of Hematology (ASH) 2018 Annual Meeting, also showed that patients administered daratumumab plus Rd over a median 28-month follow-up reported deeper responses including complete response (48% vs 25%), very good partial response (79% vs 53%), and overall response (93% vs 81%) versus lone Rd.

Patients administered the combination therapy also reported a three-fold greater rate of minimal residual disease negativity versus those on Rd (24% vs 7%).

Frequent adverse events, occurring in at least 20% of patients, included: infusion reactions; diarrhea; constipation; nausea; peripheral edema; fatigue; back pain; asthenia; pyrexia; upper respiratory tract infection; bronchitis; pneumonia; decreased appetite; muscle spams; peripheral sensory neuropathy; dyspnea; and cough.

Some of the most notable serious adverse reactions in treated patients include pneumonia (15%); bronchitis (4%); and dehydration (2%). Overall, daratumumab’s safety profile was consistent with previous findings.

The new indication could be a critical one for patients in need of a frontline therapy that could better extend their first remission period from the rare form of cancer, MAIA lead study investigator Saad Usmani, MD, of the Department of Hematologic Oncology and Blood Disorders at Levine Cancer Institute/Carolinas HealthCare System, said.

“This daratumumab 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,” Usmani said.

Craig Tendler, MD, vice president of Clinical Development and Global Medical Affairs for Janssen Research & Development Oncology, praised the approval and the potential of daratumumab to advance course-changing treatment paradigms in multiple myeloma.

"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 said in a statement.