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

Keywords:

• PCNSL
• secondary CNS lymphoma
• recurrence
• refractory
• buparlisib
• PI3K

Acknowledgements

We thank Dr. Miguel Foronda for his editorial comments.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by grants from the National Institutes of Health (P30-CA008748), the Memorial Sloan Kettering Brain Tumor Center (C.G.), the Society of Memorial Sloan Kettering Cancer Center (C.G.), the American Brain Tumor Association Basic Research Fellowship Award (C.G.), the Lymphoma Research Foundation Career Development Award (C.G.), Susan and Peter Solomon Divisional Fund (C.G.), and Cycle for Survival Equinox Innovation Award (C.G.).