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|Ref Type||Journal Article|
|Authors||Ribrag V, Kim WS, Bouabdallah R, Lim ST, Coiffier B, Illes A, Lemieux B, Dyer MJS, Offner F, Felloussi Z, Kloos I, Luan Y, Vezan R, Graef T, Morschhauser F|
|Title||Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study.|
|Abstract Text||Histone deacetylase inhibitors are members of a class of epigenetic drugs that have proven activity in T-cell malignancies, but little is known about their efficacy in B-cell lymphomas. Abexinostat is an orally available hydroxamate-containing histone deacetylase inhibitor that differs from approved inhibitors; its unique pharmacokinetic profile and oral dosing schedule, twice daily four hours apart, allows for continuous exposure at concentrations required to efficiently kill tumor cells. In this phase II study, patients with relapsed/refractory non-Hodgkin lymphoma or chronic lymphocytic leukemia received oral abexinostat at 80 mg BID for 14 days of a 21-day cycle and continued until progressive disease or unacceptable toxicity. A total of 100 patients with B-cell malignancies and T-cell lymphomas were enrolled between October 2011 and July 2014. All patients received at least one dose of study drug. Primary reasons for discontinuation included progressive disease (56%) and adverse events (25%). Grade 3 or over adverse events and any serious adverse events were reported in 88% and 73% of patients, respectively. The most frequently reported grade 3 or over treatment-emergent related adverse events were thrombocytopenia (80%), neutropenia (27%), and anemia (12%). Among the 87 patients evaluable for efficacy, overall response rate was 28% (complete response 5%), with highest responses observed in patients with follicular lymphoma (overall response rate 56%), T-cell lymphoma (overall response rate 40%), and diffuse large B-cell lymphoma (overall response rate 31%). Further investigation of the safety and efficacy of abexinostat in follicular lymphoma, T-cell lymphoma, and diffuse large B-cell lymphoma implementing a less dose-intense week-on-week-off schedule is warranted. (Trial registered at: EudraCT-2009-013691-47).|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||hematologic cancer||not applicable||Abexinostat||Phase II||Actionable||In a Phase II trial, treatment with Abexinostat (PCI-24781) in patients with a variety of hematological cancers resulted in an overall response rate (ORR) of 28% (24/87), a complete response in 5%, and a median duration response of 8.8 months (PMID: 28126962).||28126962|
|Unknown unknown||diffuse large B-cell lymphoma||not applicable||Abexinostat||Phase II||Actionable||In a Phase II trial, patients with diffuse large B-cell lymphoma demonstrated an overall response rate of 31% (5/16) and a median duration response of 1.9 months when treated with Abexinostat (PCI-24781) (PMID: 28126962).||28126962|
|Unknown unknown||lymphoma||not applicable||Abexinostat||Phase II||Actionable||In a Phase II trial, patients with T-cell lymphoma demonstrated an overall response rate of 40% (6/15) and a median duration response of 11.5 months when treated with Abexinostat (PCI-24781) (PMID: 28126962).||28126962|