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5137 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

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster III
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Adverse Events
Monday, December 9, 2024, 6:00 PM-8:00 PM

Chun-Kai Liao, MD1*, Chia-Jen Liu, MD, PhD2,3,4, Tran-Der Tan5, Ming-Chung Wang6*, Ya-Ting Hsu7*, Hung-Lin Liu8*, Shang-Ju Wu9*, Hsueh-Ju Lu10*, Jeng-Shiun Du, MD11*, Wan-Jhen Gao, MD12* and Cheng-Chih Tsai13*

1Hematology-oncology, E-DA Dachang Hospital, I-Shou University,, Kaohsiung, Taiwan
2Taipei Veterans General Hospital, Taipei, Taipei (City), TWN
3Taipei Veterans General Hospital, Taipei, Taipei (city), TWN
4Taipei Veterans General Hospital, Taipei, TWN
5Koo Foundation Sun Yat Sen Cancer Center, Taipei City, Taiwan
6Chang Gung Memorial Hospital, Kaohsiung, Taiwan
7National Cheng Kung University Hospital, Taiwan, R.O.C., TWN
8Kaohsiung-Chang Gang Memorial Hospital, Kaohsiung, TWN
9Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
10Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
11Division of Hematology/Oncology, department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
12Division of Hematology-Oncology, Chi Mei Medical Center, Tainan, TWN
13Division of Hematology and Oncology, Taitung MacKay Memorial Hospital, Taitung, Taiwan

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 >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.

Disclosures: No relevant conflicts of interest to declare.

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