In the phase II BELIEF trial reported in the Journal of Clinical Oncology, O’Connor et al found that the pan–histone deacetylase inhibitor belinostat (Beleodaq) produced durable responses in patients with relapsed/refractory peripheral T-cell lymphoma. The study supported the U.S. Food and Drug Administration’s approval of belinostat in this setting.
In the study, 120 evaluable patients from the United States, Europe, Canada, Israel, and South Africa who had disease progression after at least one prior therapy were enrolled between May 2009 and August 2011 and treated with belinostat 1,000 mg/m2 via daily 30-minute infusion on days 1 to 5 every 21 days. Overall, 88% of patients were white, 51% were male, and the median age was 64 years; patients had received a median of two prior therapies (range = 1–8); 97% had failed prior CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like therapies, and 21% had undergone prior hematopoietic stem cell transplantation.
Response was observed in 31 patients (25.8%), including complete response in 13 (10.8%) and partial response in 18 (15%). The median duration of response was 13.6 months (95% confidence interval [CI] = 4.5–29.4 months), with the longest ongoing response being > 36 months. The median duration of response in patients with complete response was not reached but was > 29 months.
The median progression-free survival was 1.6 months (95% CI = 1.4–2.7 months), and the median overall survival was 7.9 months (95% CI = 6.1–13.9 months). Stem cell transplantation was performed in 12 patients after belinostat treatment.
The most common adverse events of any grade were nausea (41.9%), fatigue (37.2%), and pyrexia (34.9%). The most common grade 3 or 4 adverse events were anemia (10.9%), thrombocytopenia (7.0%), dyspnea and neutropenia (6.2% each), and fatigue and pneumonia (5.4% each). Adverse events resulted in dose reduction in 12.4% of patients and treatment discontinuation in 19.4%. Serious adverse events occurred in 47.3%, with the most common being increased creatinine, pyrexia, and thrombocytopenia (1.6% each).
The investigators concluded: “Monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory peripheral T-cell lymphoma across the major subtypes, irrespective of number or type of prior therapies. These results have led to U.S. Food and Drug Administration approval of belinostat for this indication.”
Owen A. O’Connor, MD, PhD, of Columbia University Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by Spectrum Pharmaceuticals and Columbia University Lymphoma Research Fund. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.