FDA Approves Darzalex in Combination with Pomalidomide and Dexamethasone for Patients With Multiple Myeloma

New approval augments previous myeloma indications

The FDA has approved the immunotherapy daratumumab (Darzalex, Janssen) in combination with pomalidomide (Pomalyst, Celgene) and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide (Revlimid, Celgene) (an immunomodulatory agent) and a proteasome inhibitor (PI). Clinical trial results showed an overall response rate (ORR) of 59% with daratumumab in combination with pomalidomide and dexamethasone in these patients.

Daratumumab is the first CD-38–directed antibody approved anywhere in the world. It was first approved by the FDA in November 2015 as monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent. It received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

The new indication for daratumumab is supported by data from the phase 1b EQUULEUS trial, which showed that the combination of daratumumab with pomalidomide and dexamethasone resulted in an ORR of 59.2%, with a very good partial response achieved in 28.2% of patients. A complete response (CR) was achieved in 5.8% of patients; a stringent CR was achieved in 7.8% of patients; and partial response was achieved in 17.5% of patients. The median time to response was one month (range, 0.9–2.8 months), and the median duration of response was 13.6 months (range, 0.9–14.6 months).

Warnings and precautions in the prescribing information for daratumumab include infusion reactions; interference with cross-matching and red-blood–cell antibody screening; neutropenia; and thrombocytopenia. In the EQUULEUS trial, the most common adverse events included infusion reactions (50%), fatigue (50%), upper respiratory tract infections (50%), cough (43%), diarrhea (38%), constipation (33%), dyspnea (33%), nausea (30%), muscle spasms (26%), pyrexia (25%), back pain (25%), insomnia (23%), arthralgia (22%), vomiting (21%), and dizziness (21%), The overall incidence of serious adverse events was 49%.

The EQUULEUS trial included 103 patients with multiple myeloma who had received a prior PI and an immunomodulatory agent. Patients received 16 mg per kg of daratumumab in combination with pomalidomide and low-dose dexamethasone until disease progression. The patients’ median age was 64 years, and 8% of the patients were 75 years of age or older. The patients had received a median of four lines of therapy, and 74% had received prior autologous stem cell transplant. Ninety-eight percent of the patients received prior bortezomib treatment, and 33% received prior carfilzomib (Kyprolis, Amgen) treatment. All patients received prior lenalidomide treatment, with 98% of patients previously treated with the combination of bortezomib and lenalidomide. Eighty-nine percent of patients were refractory to lenalidomide; 71% were refractory to bortezomib; and 64% were refractory to bortezomib and lenalidomide.

Source: Janssen; June 16, 2017.