Durable Complete Remission Achieved by Tirabrutinib Rechallenge in Relapsed Primary Central Nervous System Lymphoma: A Case Report

Tirabrutinib, a second-generation Bruton tyrosine kinase inhibitor, has shown promising efficacy in patients with relapsed or refractory primary central nervous system lymphomas. However, its clinical effectiveness after a rechallenge remains largely unknown. This case report described a 59-year-old woman with primary central nervous system lymphoma who initially achieved a complete response with tirabrutinib, after discontinuing methotrexate-based chemotherapy due to treatment-related toxicity. The disease relapsed 2.5 months later, and subsequently followed a refractory course. Even high-dose chemotherapy with autologous stem cell transplantation and additional chemoradiotherapy produced only short-lived responses with repeated relapses. Tirabrutinib was re-administered as a rechallenge therapy and resulted in a fourth complete response. The patient experienced sustained complete response for 20 months while under ongoing tirabrutinib monotherapy. This case illustrates that tirabrutinib rechallenge may represent a feasible therapeutic option for select patients with recurrent primary central nervous system lymphoma, who previously received Bruton tyrosine kinase inhibitor therapy. The biological mechanisms underlying renewed drug sensitivity remain uncertain. In carefully selected cases, there may be resultant clinical benefits. Further studies are warranted to clarify the molecular and clinical determinants associated with successful tirabrutinib rechallenge in patients with primary central nervous system lymphoma.