Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma

Results of the pivotal phase II BELIEF (CLN-19) study

Owen A. O'Connor, Steven Horwitz, T. 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

Research output: Contribution to journalArticle

147 Citations (Scopus)

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/m2 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.

Original languageEnglish
Pages (from-to)2492-2499
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number23
DOIs
Publication statusPublished - Aug 10 2015

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Peripheral T-Cell Lymphoma
Disease-Free Survival
Drug Approval
Histone Deacetylase Inhibitors
belinostat
Stem Cell Transplantation
Standard of Care
Neutropenia
Thrombocytopenia
Dyspnea
Non-Hodgkin's Lymphoma
Anemia
Therapeutics
Food

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma : Results of the pivotal phase II BELIEF (CLN-19) study. / O'Connor, Owen A.; Horwitz, Steven; Masszi, T.; Van Hoof, Achiel; Brown, Peter; Doorduijn, Jeannette; Hess, Georg; Jurczak, Wojciech; Knoblauch, Poul; Chawla, Shanta; Bhat, Gajanan; Choi, Mi Rim; Walewski, Jan; Savage, Kerry; Foss, Francine; Allen, Lee F.; Shustov, Andrei.

In: Journal of Clinical Oncology, Vol. 33, No. 23, 10.08.2015, p. 2492-2499.

Research output: Contribution to journalArticle

O'Connor, OA, Horwitz, S, Masszi, T, Van Hoof, A, Brown, P, Doorduijn, J, Hess, G, Jurczak, W, Knoblauch, P, Chawla, S, Bhat, G, Choi, MR, Walewski, J, Savage, K, Foss, F, Allen, LF & Shustov, A 2015, 'Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study', Journal of Clinical Oncology, vol. 33, no. 23, pp. 2492-2499. https://doi.org/10.1200/JCO.2014.59.2782
O'Connor, Owen A. ; Horwitz, Steven ; Masszi, T. ; Van Hoof, Achiel ; Brown, Peter ; Doorduijn, Jeannette ; Hess, Georg ; Jurczak, Wojciech ; Knoblauch, Poul ; Chawla, Shanta ; Bhat, Gajanan ; Choi, Mi Rim ; Walewski, Jan ; Savage, Kerry ; Foss, Francine ; Allen, Lee F. ; Shustov, Andrei. / Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma : Results of the pivotal phase II BELIEF (CLN-19) study. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 23. pp. 2492-2499.
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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/m2 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.",
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AU - Masszi, T.

AU - Van Hoof, Achiel

AU - Brown, Peter

AU - Doorduijn, Jeannette

AU - Hess, Georg

AU - Jurczak, Wojciech

AU - Knoblauch, Poul

AU - Chawla, Shanta

AU - Bhat, Gajanan

AU - Choi, Mi Rim

AU - Walewski, Jan

AU - Savage, Kerry

AU - Foss, Francine

AU - Allen, Lee F.

AU - Shustov, Andrei

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N2 - 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/m2 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.

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