FDA Approves Belinostat for Peripheral T-Cell Lymphoma

Richard Pazdur, MD

The FDA has approved the novel pan-HDAC inhibitor belinostat (Beleodaq) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

The approval is based on results from the phase II BELIEF trial, which was conducted under an FDA Special Protocol Assessment. In the trial, treatment with belinostat elicited an overall response rate (ORR) of 26% in patients with relapsed or refractory PTCL following progression on at least one prior therapy. Patients with low platelet counts experienced responses along with a low incidence of myelosuppression, representing a potential for future combination strategies.

“This is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “Today’s approval expands the number of treatment options available to patients with serious and life-threatening diseases.”

In the single-arm BELIEF trial, 129 patients with platelets ≥ 50,000/µL and had received a median of 2 prior therapies and were evaluated. Patients received belinostat intravenously at 1000 mg/m² on days 1-5 of a 3-week cycle for a median of 2 cycles. The primary endpoint of the trial was centrally reviewed ORR. Results were presented at the 2013 ASCO Annual Meeting.

Among patients with centrally confirmed PTCL (n = 120), the ORR was 26% (CR = 10%; PR = 16%), while among patients with baseline platelets ≥100,000/μL (n = 100), the ORR was 28% (CR = 11%; PR = 17%). The median time to response was 5.6 weeks, the median duration of response was 8.3 months, and the longest duration of response in the trial was 29.4 months.

The most commonly reported side effects on this trial were nausea, fatigue, fever, low red blood cells, and vomiting, according to the FDA. The most common grade 3/4 adverse events were thrombocytopenia (13%), neutropenia (13%), anemia (10%), dyspnea (6%), pneumonia (6%), and fatigue (5%).

“Since approximately 70% of R/R PTCL patients fail the currently approved treatments in the course of their therapy, Beleodaq could be an important additional treatment option for these patients,” Rajesh C. Shrotriya, MD, chairman, chief executive officer, and president of Spectrum Pharmaceuticals, said in a statement following the announcement of the priority review. “Importantly, several patients treated with Beleodaq were able to go on to potentially curative stem cell transplantation.”

Belinostat is also being investigated in non-small cell lung cancer as well as other solid and hematologic tumors. In trials outside of PTCL, belinostat is commonly administered in combination with carboplatin and paclitaxel.