Final three-year follow-up analysis of phase I/II study on tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma.

Abstract

7548 Background: Primary central nervous system lymphoma (PCNSL) is known as an uncommon and extremely aggressive type of non-Hodgkin lymphoma of brain tumors. Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for the treatment of relapsed or refractory PCNSL (rrPCNSL) based on the results of phase I/II study in Japan (Trial registration: JapicCTI-173646) in 2020. Methods: In this study, 44 Japanese patients with rrPCNSL received TIR QD at doses of 320 mg (n = 20), 480 mg (n = 7), or 480 mg while fasting (480 mg fasted: n = 17). The International PCNSL Collaborative Group criteria were used to assess the primary endpoint, which was the overall response rate (ORR). We previously reported the interim results with 14.9 (range:1.4–27.7) months of median follow-up in 2020 (Mishima et al., the 25th Society for Neuro-Oncology 2020). The final analysis results with a three-year follow-up are reported here (data cutoff: April 27th, 2022). Results: For the entire population, the ORR was 63.6% with 36.4% of complete response, the median duration of response was 9.2 months, the median progression-free survival was 2.9 months, and the median overall survival was not reached (median follow-up: 37.1 months). The most frequent adverse events (AEs) were skin and subcutaneous tissue disorders and blood and lymphatic system disorders at any grade, including rash (36.4%) and neutropenia (27.3%), leukopenia (25.0%), lymphopenia (18.2%), and thrombocytopenia (11.4%). Grade ≥3 AEs were neutropenia (9.1%), leukopenia (9.1%), lymphopenia (6.8%), and erythema multiforme (6.8%). One patient with 480 mg had grade 5 AEs (Pneumocystis jirovecii pneumonia and Interstitial lung disease), while neither new grade 5 AEs nor new safety profiles were observed since the last data cutoff. As of the current data cutoff, 15 and 6 of 44 patients had been receiving TIR for more than one and three years, respectively, and 5 of the 6 patients continued receiving TIR, including 4 patients who were receiving 480 mg fasted. Conclusions: In conclusion, TIR showed long-lasting effectiveness in a subset of patients with a tolerable safety profile of rrPCNSL. Clinical trial information: JapicCTI-173646. [Table: see text]