BTK Inhibitors in Relapsed/Refractory Primary CNS Lymphoma

Dr. Christian Grommes discusses the emerging role of BTK inhibitors in relapsed/refractory primary CNS lymphoma (PCNSL), focusing on U.S. off-label use and ongoing clinical investigation. He reflects on phase 1/2 experience with ibrutinib, which demonstrated response rates above 70% and a progression-free survival of approximately 4 to 5 months in PCNSL, contrasting with the more limited activity observed with ibrutinib in systemic diffuse large B-cell lymphoma. Dr. Grommes notes that these findings helped establish BTK inhibition as an area of interest in CNS lymphoma and contributed to its inclusion in NCCN guidance for recurrent/refractory PCNSL. He describes ongoing studies evaluating BTK inhibitors in combination with agents such as rituximab, lenalidomide, and other novel therapies, as well as investigations of second-generation agents including acalabrutinib and zanubrutinib. In U.S. practice, he identifies ibrutinib and zanubrutinib as commonly used off-label options, with treatment selection influenced in part by adverse-event considerations. In particular, the potential for atrial fibrillation and bleeding with ibrutinib is highlighted as an important consideration in the predominantly older PCNSL population.