Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma
| Autor: | Gilles Salles, John F. Gerecitano, Eva González Barca, Robert G. Bociek, Chaitali Babanrao Pisal, Ranjana Tavorath, Mehmet Turgut, Giovanni Martinelli, Anas Younes, Won Seog Kim, Dolores Caballero Barrigon, O Kong |
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| Přispěvatelé: | OMÜ |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Pathology Morpholines Non-Hodgkin Lymphoma Population Follicular lymphoma Buparlisib Aminopyridines Lymphoma Mantle-Cell Neutropenia Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Refractory Non-Hodgkin Lymphoma Recurrence immune system diseases Internal medicine hemic and lymphatic diseases medicine Humans education Lymphoma Follicular Aged Phosphoinositide-3 Kinase Inhibitors Aged 80 and over Salvage Therapy education.field_of_study business.industry Lymphoma Non-Hodgkin Remission Induction Hematology Middle Aged medicine.disease Lymphoma Malaltia de Hodgkin 030104 developmental biology Tolerability chemistry 030220 oncology & carcinogenesis Female Mantle cell lymphoma Lymphoma Large B-Cell Diffuse Hodgkin's disease business |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname Haematologica |
| Popis: | Martinelli, Giovanni/0000-0002-1025-4210; BARCA, EVA GONZALEZ/0000-0002-1323-1508 WOS: 000416867100031 PubMed: 28971900 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. Novartis Pharmaceuticals CorporationNovartis We would also like to thank Nabanita Mukherjee for support with the statistical analysis, Joe Sulovski for trial design, study conduct, and review of early versions of the manuscript, Fabian Herbst for review of early versions of the manuscript, and Pamela Tuttle, PhD, CMPP, and Katherine Mills-Lujan, PhD, of ArticulateScience, LLC for medical editorial assistance, which was funded by Novartis Pharmaceuticals Corporation. |
| Databáze: | OpenAIRE |
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