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

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

Research output: Contribution to journalArticle

21 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

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