Identifying patterns of failure after initial therapy in primary cns lymphoma in a large patient cohort

Abstract INTRODUCTION Treatment of primary CNS lymphoma (PCNSL) has rapidly evolved, emphasizing improved efficacy while reducing neurotoxicity. PCNSL has historically been considered a multifocal disease and many patients relapse after first-line therapy. We evaluated relapse patterns in a large cohort of contemporarily treated patients. METHODS Consecutive PCNSL patients treated at MSKCC between 1983-2020 were analyzed. T1 post-contrast-enhancing disease on baseline MRI was characterized. Site of initial relapse was characterized as purely local (involving/adjacent to initial site) vs distant intraparenchymal, or other (e.g., both local and distant, systemic, ocular). Progression-free survival (PFS) was evaluated using Kaplan Meier methods. RESULTS Of 645 patients, 564 were eligible for analysis (diffuse large B-cell histology, sufficient data, ≥ 1 MRI response assessment). Median follow-up was 2.7 years (IQR 1.2-5.6). Median age was 63 years (range 19-90). Baseline disease was often supratentorial (420, 74%), multifocal (274, 49%), and bilateral (224, 40%). Fewer had leptomeningeal disease (94/430 CSF+, 22%; 117/559 radiographically positive, 21%). Most received methotrexate (MTX)-based induction (534, 96%), most commonly rituximab, MTX, procarbazine, vincristine (R-MVP; 257, 46%) or MVP (144, 26%). Overall, 286 (51%) patients relapsed with a median PFS of 2.1 years (95% CI 1.8-2.5). Of 275 characterizable relapses, 75 (27%) were exclusively local intraparenchymal, 91 (33%) were distant intraparenchymal, and 109 (40%) were other. Baseline unifocal disease often relapsed unifocally (66/118 baseline unifocal; 56%). Of 126 unifocal relapses, 45 (36%) were local. Of 202 patients with baseline supratentorial disease, 152 (75%) relapsed supratentorially. Unilateral relapses often remain ipsilateral (49% left- and 54% right-hemispheric lesions at baseline and relapse). CONCLUSIONS In a large PCNSL cohort, relapses often maintained baseline characteristics. For a disease historically considered multifocal, a substantial proportion of relapses were local. Future analyses will evaluate predictors of relapse, which can further efforts in informing personalization of treatment in the era of cellular therapies.