Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma Journal Article
| Authors: | Younes, A.; Salles, G.; Martinelli, G.; Bociek, R. G.; Barrigon, D. C.; González Barca, E.; Turgut, M.; Gerecitano, J.; Kong, O.; Pisal, C. B.; Tavorath, R.; Kim, W. S. |
| Article Title: | 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 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). © 2017 Ferrata Storti Foundation. |
| Keywords: | survival; adult; major clinical study; fatigue; pathogenesis; drug safety; mantle cell lymphoma; nausea; hemoglobin; histology; hodgkin disease; hyperglycemia; b cell lymphoma; rapamycin; hematology; phosphatidylinositol 3 kinase inhibitor; buparlisib; human; male; article; follicular lymphoma cell line; non-hodgkin lymphoma cell line |
| Journal Title: | Haematologica |
| Volume: | 102 |
| Issue: | 12 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2017-11-30 |
| Start Page: | 2104 |
| End Page: | 2112 |
| Language: | English |
| DOI: | 10.3324/haematol.2017.169656 |
| PROVIDER: | scopus |
| PMCID: | PMC5709110 |
| PUBMED: | 28971900 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 January 2018 -- Source: Scopus |
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