An Update on Treatments for Recurrent Primary Central Nervous System Lymphoma

Purpose of Review: Recurrent primary central nervous system lymphoma (PCNSL) has remained a challenging disease to treat with high rates of relapse with relatively short remissions. The purpose of this review was to assess the current landscape of treatment for recurrent PCNSL. Recent Findings: Clinical trials have investigated treatments including methotrexate regimens, Bruton’s tyrosine kinase inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, CAR-T, IRAK4 inhibitors, bispecific antibodies, and other targeted agents. Despite significant overall response rates (ORR), most studies yielded short nondurable remissions. More recent trials have therefore pursued combination of these novel agents. Preliminary data from selected active trials for recurrent PCNSL have indicated notable ORRs ranging from 50 to 94% and tolerable safety profiles. Summary: Novel treatments have shown promise in treatment for recurrent PCNSL, significantly increasing available options at recurrence. Due to nondurable monotherapy responses, combination therapy of investigational agents has emerged as a consensus path forward for future clinical trials.