Daratumumab Granted FDA Approval for Treatment-Resistant Multiple Myeloma

November 17, 2015

On November 16, 2015, the US Food and Drug Administration (FDA) approved daratumumab (Darzalex) to treat patients with multiple myeloma who have received at least three prior treatments.

On November 16, 2015, the US Food and Drug Administration (FDA) approved daratumumab (Darzalex) to treat patients with multiple myeloma who have received at least three prior treatments.

Daratumumab is the first monoclonal antibody approved for treating multiple myeloma--a cancer that forms in plasma cells. This unusual hematologic disorder causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood cells.

Daratumumab is the first human anti-CD38 monoclonal antibody (mAb) approved and it works by inducing tumor cell death through multiple immune-mediated mechanisms of action. CD38 is a surface protein that is expressed by multiple myeloma cells.

“Targeting proteins that are found on the surface of cancer cells has led to the development of important oncology treatments,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, in a press release.

The phase II MMY2002 (SIRIUS) study showed treatment with single-agent daratumumab resulted in an overall response rate (ORR) of 29.2% in patients who received five prior lines of therapy, which included proteasome inhibitors (PI) and immunomodulatory agents (IMiD). Stringent complete response (sCR) was reported in 2.8% of patients, very good partial response (VGPR) was reported in 9.4% of patients, and partial response (PR) was reported in 17% of patients. The median duration of response was 7.4 months.

At baseline, 97% of patients were refractory to their last line of therapy, 95% were refractory to both a PI and an IMiD, and 77% were refractory to alkylating agents. Sixty-three percent were refractory to pomalidomide (Pomalyst), and 50% were refractory to carfilzomib (Kyprolis).

“The responses we saw in clinical trials that led to today’s approval were striking, especially considering that these patients received a median of five prior lines of therapy,” said study investigator Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University and Professor and Executive Vice Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine, in a press release.

The recommended dose of daratumumab is 16 mg/kg administered as an intravenous infusion. The dosing schedule begins with weekly administration (weeks 1-8) and reduces in frequency over time to every 2 weeks (weeks 9-24), and then every 4 weeks going forward until disease progression.

Side effects included infusion-related reactions, fatigue, nausea, back pain, fever, and cough. This treatment may also cause lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia.

There will be 26,850 new cases of multiple myeloma and 11,240 related deaths in the United States this year according to the National Cancer Institute, so it is crucial that new treatments like this are being developed, tested, and approved.