Real World Evidence of Tirabrutinib As a Salvage Treatment in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma in Taiwan: A Multicenter Study
Authors: Liao Chun-Kai , Liu Chia-Jen , Tan Tran-Der , Wang Ming-Chung , Hsu Ya-Ting , Liu Hung-Lin , Wu Shang-Ju , Lu Hsueh-Ju , Du Jeng-Shiun , Gao Wan-Jhen , Tsai Cheng-Chih 
Published: December 2024

Background: Relapsed or refractory primary central nervous system lymphoma (r/r PCNSL) is a challenging brain tumor with a poor prognosis. Tirabrutinib was approved in Taiwan in February 2022 as a salvage therapy based on favorable results from the phase I/II study (ONO-4059-02). However, real-world data on its efficacy and safety remain limited.
Aims: This study aims to evaluate the effectiveness and safety profiles of tirabrutinib in real-world settings for patients with r/r PCNSL, particularly focusing on hepatitis B virus (HBV) reactivation.
Methods: We conducted a retrospective analysis of clinical data from patients with r/r PCNSL who received tirabrutinib under a compassionate use program between July 2021 and December 2023. Data collected included baseline characteristics, laboratory results, adverse drug reactions (ADRs), HBV infection status, survival and overall response rates (ORR). The ORR was evaluated according to the criteria of the International PCNSL Collaborative Group (IPCG). The timing and method of imaging study was at discretion of physician.
Results: At the end of 2023, 18 patients from 9 hospitals in Taiwan were enrolled. One patient was only included in safety analysis because not met tirabrutinib Taiwan approved indication. Of the 17 patients, 9 (59%) were male. Their median age was 63 years (26-88 years). The ECOG Performance Status scores were 0-1 for 7 patients (41%), 2 for 5 patients (29%), and &gt;3 for 5 patients (30%). The median number of previous lines of treatment was 3 (range, 1-4) and tirabrutinib was third line or beyond for most patients (n=14, 82%). The median duration of tirabrutinib treatment was 4 months (0.6-28 months); 4 patients (24%) continued taking tirabrutinib over 1 year and until the end of the observation period. Of the 12 patients who discontinued Tirabrutinib treatment, 3 (25%) did so because of disease progression, 5 (41%) because of adverse events (ADRs), 2 (17%) expired due to comorbidities, and 2 (17%) for other reasons. The most common hematological ADRs were neutropenia (n=7; 39%) with grade 3 neutropenia in 4 patients (22%) and thrombocytopenia (n=7, 39%; 17% worse than grade 3). Infections were observed in 6 patients (33%) and all were worse than grade 3, including 1 patient die of septic shock and 1 with cov-19 infection. Grade 1 or 2 bleeding was observed in 2 patients (11%). One patient was found to have liver function impairment and 1 patient with HBV reactivation without antiviral agent prophylaxis. Atrial fibrillation was found in 1 patient.
The overall response was 64% and rate of confirmed or unconfirmed complete response rates were 29% and 12%, respectively. With the median follow-up time of 15.9 (10.0-21.7) months, the median progression-free survival (PFS) was 4.9 (0 - 15.4) months and median overall survival(OS) were 13.4 (3.1 - 23.7) months. Patients who were responsive to tirabrutinib had a longer PFS (median 11.4 vs. 1.0 months; HR=0.59, 95% CI: 0.00-7.80; p=0.02) with no significant difference in OS (median NE vs. 6.4 months; HR=0.61, 95% CI: 3.1-23.69; p=0.18).
Conclusion: In this real-world study, tirabrutinib demonstrated efficacy as a salvage therapy for r/r PCNSL. Infection remains a significant safety concern, although dermatological ADRs were less prevalent compared to clinical trials. With optimal prophylaxis, the risk of HBV reactivation was not a major concern.Keywords: Tirabrutinib, r/r PCNSL, real-world data, efficacy, safety, HBV reactivation.