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 M.; Masszi, Tamás; Hoof, A. van; Brown, Peter de Nully; Doorduijn, J.; Heß, Georg; Jurczak, Wojciech; Knoblauch, Poul; Chawla, Santa; Bhat, Gajanan; Choi, Mi Rim; Walewski, Jan; Savage, Kerry J.; Foss, Francine M.; Allen, Lee F.; Shustov, Andrei R.

doi:10.1200/jco.2014.59.2782

Cited by 417 publications

(288 citation statements)

References 35 publications

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“…A third inhibitor, the pan-HDAC inhibitor Belinostat, was also more recently approved for relapsed and refractory PTCL cases [160,161]. The overall responses were 25% for Romidepsin and 26% for Belinostat [162,163]. Additional indications for Romidepsin are currently being evaluated as a combinatorial treatment, for instance, with Bortezomib, Carfilzomib (both proteasome inhibitors), 5-Azacytidine, or CHOP.…”

Section: Current Therapies and Novel Approachesmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

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Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools.

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Section: Current Therapies and Novel Approachesmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

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“…Results led to CFDA approval of chidamide in relapsed or refractory PTCL in December 2014.The full report of the pivotal phase II study can be found in a recent publication (22). It would be interesting to compare the results of chidamide with the other three FDA approved PTCL drugs, all derived from their pivotal phase II trials (7)(8)(9)22). While there were similar patient baseline characteristics from these trials in terms of age, gender, years since first diagnosis and prior systemic therapy numbers, a significant difference presented in the pathological subtypes of patients enrolled between the chidamide trial and the others (Table 3).…”

Section: Pivotal Phase II Trialmentioning

confidence: 99%

Development of chidamide for peripheral T-cell lymphoma, the first orphan drug approved in China

Lu¹,

Ning²,

Li³

et al. 2016

IRDR

145

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“…The adverse reaction profile was similar in the BELIEF trial, which is one of the largest safety analyses of belinostat currently available. 22 The most common grade 3/4 adverse events observed in the 120 patients included were thrombocytopenia and neutropenia, occurring in 13% of the patients, respectively. Anemia (10%), dyspnea (6%), pneumonia (6%), and fatigue (5%) were the other common grade 3/4 adverse reactions observed.…”

Section: Safetymentioning

confidence: 99%

“…22 In this single-arm, Phase II clinical trial, patients were eligible for enrollment after failing at least one prior treatment. The primary study objective was to assess the safety and efficacy of single-agent belinostat in refractory or relapsed PTCL.…”

mentioning

confidence: 99%

Critical appraisal of belinostat in the management of T-cell lymphoma – patient considerations

Bodiford¹,

Talbott²,

Reddy³

2015

BLCTT

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Abstract:The histone deacetylase inhibitor (HDACi), belinostat, is an emerging and novel therapeutic option for patients diagnosed with relapsed/refractory peripheral T-cell lymphoma (PTCL). The PTCLs are comprised of multiple subtypes that occur in less than one per 100,000 cases in the USA. The incidence of these malignancies is rare, thus limited evidence is available. The most appropriate treatment modality has not been established. The most current recommended option is combination chemotherapy or enrollment in a clinical trial. T-cell lymphomas have emerged as a disease with marked epigenetic dysregulation. HDACi are an innovative and emerging medication class gaining increased attention in the treatment of T-cell lymphomas. There is a need to evaluate their potential place in the treatment of patients diagnosed with PTCL. Currently, the largest study evaluating belinostat use in this patient population is the BELIEF study. The BELIEF study is a single-arm, Phase II clinical trial, evaluating the use of belinostat in patients with refractory or relapsed PTCL. The primary outcome, objective response rate, was 26%, with 11% achieving a complete response and 15% a partial response. This study presents a potential novel therapeutic option in the treatment of these patients. In this paper, we review therapeutic options for PTCL and present the recent data on the role of HDACi, specifically belinostat, in the treatment of patients with relapsed/refractory PTCL.

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

Cited by 417 publications

References 35 publications

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Development of chidamide for peripheral T-cell lymphoma, the first orphan drug approved in China

Critical appraisal of belinostat in the management of T-cell lymphoma – patient considerations

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

Cited by 417 publications

References 35 publications

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Development of chidamide for peripheral T-cell lymphoma, the first orphan drug approved in China

Critical appraisal of belinostat in the management of T-cell lymphoma &ndash; patient considerations

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Critical appraisal of belinostat in the management of T-cell lymphoma – patient considerations