Faculty, Staff and Student Publications

Publication Date

4-8-2025

Journal

Blood Advances

Abstract

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years unless progression or unacceptable toxicity occurred. A total of 18 patients were enrolled with a median age of 63 years (range, 43-88). The median number of previous lines of therapy was 2 (range, 1-4); 55% had refractory disease, 17% previously underwent stem cell transplant, and 11% previously underwent chimeric antigen receptor T-cell therapy. The best overall response rate was 78% and the best complete response rate was 50% (95% confidence interval, 26-74). The median progression-free survival and overall survival was 6.5 months and 21.0 months, respectively, and 3 patients continued to be in remission for >2 years. Treatment was generally well tolerated but 2 patients stopped treatment because of fatigue. Ibrutinib and nivolumab had reasonable safety and clinical activity in patients with refractory/relapsed CNS lymphoma and warrants further investigation. This trial was registered at www.ClinicalTrials.gov as #NCT03770416.

Keywords

Humans, Adenine, Middle Aged, Central Nervous System Neoplasms, Male, Female, Nivolumab, Aged, Adult, Piperidines, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Lymphoma, Treatment Outcome, Recurrence

DOI

10.1182/bloodadvances.2024014635

PMID

39908461

PMCID

PMC11985036

PubMedCentral® Posted Date

2-19-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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