Preclinical and clinical evaluation of Buparlisib (BKM120) in recurrent/refractory Central Nervous System Lymphoma Journal Article
| Authors: | Grommes, C.; Pentsova, E.; Schaff, L. R.; Nolan, C. P.; Kaley, T.; Reiner, A. S.; Panageas, K. S.; Mellinghoff, I. K. |
| Article Title: | Preclinical and clinical evaluation of Buparlisib (BKM120) in recurrent/refractory Central Nervous System Lymphoma |
| Abstract: | Central Nervous System (CNS) Lymphomas are aggressive brain tumors with limited treatment options. Targeting the phosphoinositide 3-kinase (PI3K) pathway yields promising responses across B-cell malignancies, but its therapeutic potential in CNS lymphomas remains unexplored. We present pre-clinical and clinical data on the pan-PI3K inhibitor Buparlisib in CNS lymphomas. In a primary CNS lymphoma-patient-derived cell line, we define the EC50. Four patients with recurrent CNS lymphoma were enrolled in a prospective trial. We evaluated Buparlisib plasma and cerebrospinal fluid pharmacokinetics, clinical outcomes, and adverse events. Treatment was well tolerated. Common toxicities include hyperglycemia, thrombocytopenia, and lymphopenia. The presence of Buparlisib in plasma and CSF was confirmed 2h post-treatment with a median CSF concentration below the EC50 defined in the cell line All four patients were evaluated for response and the median time to progression was 39 days. Buparlisib monotherapy did not lead to meaningful responses and the trial was prematurely stopped.Clinical Trial Registration: NCT02301364. © 2023 Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | adult; clinical article; controlled study; human cell; overall survival; clinical trial; fatigue; neutropenia; cancer recurrence; cancer growth; drug withdrawal; monotherapy; nonhuman; side effect; nuclear magnetic resonance imaging; prospective study; prospective studies; mouse; animal tissue; progression free survival; neutrophil count; neoplasm recurrence, local; thrombocytopenia; clinical assessment; animal experiment; animal model; recurrence; in vitro study; tumor xenograft; phosphatidylinositol 3 kinase; central nervous system; hyperglycemia; lymphocytopenia; pruritus; chronic disease; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; maculopapular rash; depression; drug distribution; lumbar puncture; blood sampling; lymphoma, non-hodgkin; tumor recurrence; cancer size; lymphoma; brain disease; cognitive defect; cholesterol; seizure; drug blood level; memory disorder; dry skin; hallucination; leukocyte; myeloid differentiation factor 88; lymphocyte count; pi3k; non-hodgkin lymphoma; hospice care; refractory; deterioration; drug cerebrospinal fluid level; clinical outcome; phosphatidylinositol 3-kinases; overall response rate; pcnsl; buparlisib; humans; human; male; female; article; aminopyridines; aminopyridine derivative; concentration at steady-state; ec50; central nervous system cancer; nvp-bkm120; cd79b antigen; secondary cns lymphoma |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 64 |
| Issue: | 9 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2023-01-01 |
| Start Page: | 1545 |
| End Page: | 1553 |
| Language: | English |
| DOI: | 10.1080/10428194.2023.2223734 |
| PUBMED: | 37317993 |
| PROVIDER: | scopus |
| PMCID: | PMC10529084 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Christian Grommes -- Source: Scopus |
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