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

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 lymphoma) 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).

• Authors: 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
• Journal: Haematologica (Haematologica) Vol. 102 Issue 12 Pg. 2104-2112 (12 2017) ISSN: 1592-8721 [Electronic] Italy
• PMID: 28971900 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright© 2017 Ferrata Storti Foundation.

Chemical References

• Aminopyridines
• Morpholines
• NVP-BKM120
• Phosphoinositide-3 Kinase Inhibitors

Topics

• Adult
• Aged
• Aged, 80 and over
• Aminopyridines (adverse effects, pharmacology, therapeutic use)
• Female
• Humans
• Lymphoma, Follicular (complications, drug therapy)
• Lymphoma, Large B-Cell, Diffuse (complications, drug therapy)
• Lymphoma, Mantle-Cell (complications, drug therapy)
• Lymphoma, Non-Hodgkin (complications, drug therapy)
• Male
• Middle Aged
• Morpholines (adverse effects, pharmacology, therapeutic use)
• Phosphoinositide-3 Kinase Inhibitors
• Recurrence
• Remission Induction
• Salvage Therapy (methods)