Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study.

Abstract

PURPOSE:

Peripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL.

PATIENTS AND METHODS:

Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m(2) as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included duration of response (DoR) and progression-free and overall survival.

RESULTS:

A total of 129 patients were enrolled, with a median of two prior systemic therapies. Overall response rate in the 120 evaluable patients was 25.8% (31 of 120), including 13 complete (10.8%) and 18 partial responses (15%). Median DoR by International Working Group criteria was 13.6 months, with the longest ongoing patient at ≥ 36 months. Median progression-free and overall survival were 1.6 and 7.9 months, respectively. Twelve of the enrolled patients underwent stem-cell transplantation after belinostat monotherapy. The most common grade 3 to 4 adverse events were anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), and neutropenia (6.2%).

CONCLUSION:

Monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication.

• Authors: Owen A O'Connor, Steven Horwitz, Tamás Masszi, Achiel Van Hoof, Peter Brown, Jeannette Doorduijn, Georg Hess, Wojciech Jurczak, Poul Knoblauch, Shanta Chawla, Gajanan Bhat, Mi Rim Choi, Jan Walewski, Kerry Savage, Francine Foss, Lee F Allen, Andrei Shustov
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 23 Pg. 2492-9 (Aug 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26101246 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Sulfonamides
• belinostat

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Histone Deacetylase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Humans
• Hydroxamic Acids (administration & dosage, adverse effects, therapeutic use)
• Infusions, Intravenous
• Kaplan-Meier Estimate
• Lymphoma, T-Cell, Peripheral (drug therapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Sulfonamides (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome