Glofitamab with polatuzumab vedotin in relapsed/refractory central nervous system lymphomas

Patients with relapsed/refractory (r/r) central nervous system lymphoma (CNSL) have poor survival with currently available treatments. Early reports suggest antibody-based treatments such as bispecific antibodies and antibody-drug conjugates can penetrate the blood-brain barrier and induce clinical responses in r/r CNSL. In this study, we retrospectively evaluated the safety and activity of glofitamab plus polatuzumab vedotin in 9 r/r CNSL patients treated at our institution, including high-risk subtypes such as chemorefractory Burkitt lymphoma and TP53-mutant Mantle cell lymphoma. Here, we observed a 100% overall and 89% complete response rate. Responses occurred in patients with brain parenchymal and leptomeningeal involvement, with rapid clearance of lymphoma cells from the cerebrospinal fluid within days of treatment as assessed by flow cytometry. Safety aligned with the known toxicity profile of the regimen in patients with systemic lymphomas. These data indicate glofitamab with polatuzumab vedotin is capable of safely inducing deep and rapid clinical remissions in r/r CNSL, including in high-risk histological and molecular subtypes. Future prospective evaluation of the regimen for r/r CNSL is warranted given the unmet need of this population.