Abstract
Belinostat induces durable responses and is well tolerated in patients with relapsed or refractory PTCL.
Major finding: Belinostat induces durable responses and is well tolerated in patients with relapsed or refractory PTCL.
Concept: T-cell lymphomas exhibit epigenetic defects and are sensitive to pan-HDAC inhibitors.
Impact: The combination of belinostat with other therapeutic regimens may improve outcome in PTCL.
Current treatments for peripheral T-cell lymphoma (PTCL), a group of aggressive non-Hodgkin lymphomas associated with poor prognosis, fail to induce clinical responses in many cases, and patients frequently experience tumor relapse. Previous studies have indicated that T-cell lymphomas are often characterized by mutations in epigenetic regulators and exhibit sensitivity to histone deacetylase (HDAC) inhibitors, prompting O'Connor and colleagues to evaluate the efficacy and safety of the pan-HDAC inhibitor belinostat in PTCL in a phase II clinical trial. The response to single-agent treatment with belinostat was assessed in 120 patients with relapsed or refractory PTCL, many of whom had received multiple prior systemic therapies. Belinostat treatment resulted in an overall response rate of 25.8% (31 of 120 patients) and induced complete responses in 13 (10.8%) patients and partial responses in 18 (15%) patients; median progression-free survival was 1.6 months and median overall survival was 7.9 months. In addition, 63.3% of patients exhibited decreased tumor volume, and belinostat treatment enabled 12 patients to undergo hematopoietic stem cell transplant. These responses were observed across PTCL subtypes and were durable, with a median duration of response of 13.6 months and an ongoing response greater than 36 months in one patient. Belinostat monotherapy was well tolerated and generally resulted in mild to moderate adverse events that did not require dose reductions; the most common grade 3–4 treatment-related toxicities were anemia, thrombocytopenia, dyspnea, and neutropenia. These findings demonstrating the antitumor activity of belinostat resulted in its recent approval by the FDA for patients with relapsed or refractory PTCL and suggest that the combination of belinostat with other therapeutic agents may improve clinical outcomes in PTCL.
Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
RSS Feeds