ML-10 Tirabrutinib, a second-generation BTK inhibitor in relapsed and refractory primary CNS lymphoma: A single institute study

Abstract BACKGROUND: The prognosis of relapsed and refractory (r/r) primary CNS lymphoma (PCNSL) is poor, and the development of new therapeutic agents is desirable. Comprehensive genetic analysis of PCNSL has shown that MYD88 and CD79B are frequently mutated and are oncogenic drivers, suggesting that Bruton’s tyrosine kinase (BTK), which is located downstream of MYD88 and CD79B, may be a reasonable therapeutic target. Tirabrutinib is a second-generation oral BTK inhibitor recently approved in Japan for the treatment of r/r PCNSL. In this study, we evaluated the efficacy and safety of tiraburtinib treatment of r/r PCNSL at Saitama Medical University. MATERIAL AND METHODS: Eighteen patients with r/r PCNSL to HD-MTX-based regimens were treated with 480 mg tiraburtinib daily under fasting conditions until disease progression. RESULTS: The median age was 63.5 years, and the median KPS was 70. Nine patients (50%) achieved a CR, 2 (11%) had a partial response, 3 (17%) had stable disease, and 4 (22%) had progressive disease. After a median follow-up of 17.3 months, the median progression-free survival was 7.9 months, and the median overall survival was 23.6 months. There were four cases of long-term treatment lasting more than one year. Grade 3 or higher adverse events were observed in 1 case of maculopapular rash, 1 case of cardiac failure, 1 case of neutropenia, and 1 case of lymphopenia. CONCLUSION: Tiraburtinib can be administered relatively safely to patients with relapsed or refractory PCNSL, and a certain degree of efficacy can be expected. Which patients can be treated with tiraburtinib over the long term, when can stop tirabrutinib treatment for patients with long-term CR, and the mechanism of tiraburtinib resistance needs to be determined.