Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma

Anas Younes, Gilles Salles, Giovanni Martinelli, Robert G Bociek, Dolores Caballero Barrigon, Eva González Barca, Mehmet Turgut, John Gerecitano, Oliver Kong, Chaitali Babanrao Pisal, Ranjana Tavorath, Won Seog Kim

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16 Scopus citations

Abstract

Activation of the phosphatidylinositol 3-kinase/mechanistic target of rapamycin pathway plays a role in the pathogenesis of non-Hodgkin lymphoma. This multicenter, open-label phase 2 study evaluated buparlisib (BKM120), a pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or refractory non-Hodgkin lymphoma. Three separate cohorts of patients (with diffuse large B-cell lymphoma, mantle cell lymphoma, or follicular lymphoma) received buparlisib 100 mg once daily until progression, intolerance, or withdrawal of consent. The primary endpoint was overall response rate based on a 6-month best overall response by cohort; secondary endpoints included progression-free survival, duration of response, overall survival, safety, and tolerability. Overall, 72 patients (26 with diffuse large B-cell lymphoma, 22 with mantle cell lymphoma, and 24 with follicular lym-phoma) were treated. The overall response rates were 11.5%, 22.7%, and 25.0% in patients with diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, respectively; two patients (one each with diffuse large B-cell lymphoma and mantle cell lymphoma) achieved a complete response. The most frequently reported (>20%) adverse events of any grade in the population in which safety was studied were hyperglycemia, fatigue, and nausea (36.1% each), depression (29.2%), diarrhea (27.8%), and anxiety (25.0%). The most common grade 3/4 adverse events included hyperglycemia (11.1%) and neutropenia (5.6%). Buparlisib showed activity in relapsed or refractory non-Hodgkin lymphoma, with disease stabilization and sustained tumor burden reduction in some patients, and acceptable toxicity. Development of mechanism-based combination regimens with buparlisib is warranted. (This study was funded by Novartis Pharmaceuticals Corporation and registered with ClinicalTrials.gov number, NCT01693614).

Original languageEnglish (US)
Pages (from-to)2104-2112
Number of pages9
JournalHaematologica
Volume102
Issue number12
DOIs
StatePublished - Nov 30 2017

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ASJC Scopus subject areas

  • Hematology

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Younes, A., Salles, G., Martinelli, G., Bociek, R. G., Barrigon, D. C., Barca, E. G., Turgut, M., Gerecitano, J., Kong, O., Pisal, C. B., Tavorath, R., & Kim, W. S. (2017). Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma. Haematologica, 102(12), 2104-2112. https://doi.org/10.3324/haematol.2017.169656