BTK and primary central nervous system lymphoma: BTK inhibition has proven quite successful when used as a single agent in PCNSL (primary central nervous system DLBCL) and secondary CNSL,203, 204, 205 with clinical response seen in 78% of CNS lymphoma patients in a phase II study.204 An Ibrutinib/Methotrexate/Rituximab combination has shown manageable toxicity and promising results in relapsed/refractory CNS lymphomas with 80% clinical response rate in a phase Ib trial.204