Impact of systemic therapy regimen on survival of PCNSL.

Abstract

2070 Background: Primary CNS Lymphoma (PCNSL) is a rare and often fatal disease. Treatment includes multi-agent systemic therapy with a backbone of high-dose methotrexate (HD-MTX). Despite multiple drug and radiotherapy combinations for induction and consolidation treatment there remains no clear standard of care. The purpose of this analysis is to evaluate how varying treatment approaches impacted clinical outcomes at our institution. Methods: Data retrospectively collected for 95 consecutive patients with PCNSL pathologically confirmed from 2002 to 2021. Primary endpoint was OS with secondary endpoints of PFS and LC. Progression based on RANO criteria. Kaplan-Meier analyses, Log-rank test and Cox proportional hazard models used for time to event endpoints. MVA by backward selection applying an alpha of 0.2 for associations with 1st line chemo agents, number of cycles of HD-MTX (>6 or 0-5), size of enhancing tumor at presentation, CSF cytology, type of surgery (biopsy, STR, or GTR), and use of WBRT. Results: Most patients had KPS >70 (64.2%), were HIV negative (89.5%), and had no history of solid organ transplant (95.8%). Diagnosis was made by biopsy (73.7%) or resection (GTR 13.7%, STR 12.6%). 54.3% had <14 cc contrast-enhancing tumor volume (median 12.6 cc, range 0.5 - 67.8 cc) and 48.6% had single enhancing lesion. Of the 62 patients treated first line with at least 1 cycle of HD-MTX, 61.3% were treated with HD-MTX + Rituximab (R) and 33.9% with HD-MTX + R + temozolomide (TMZ). With or after induction HD-MTX, 1-3 patients received one or a combination of cytarabine, thiotepa, procarbazine, vincristine, carmustine, or ASCT. Of the 60 patients with evaluable CSF, 30.0% had positive cytology. IT chemotherapy (ITc) was administered to 12 patients (5 with + cytology, 4 with - cytology, 3 with unknown cytology). WBRT for consolidation after chemotherapy used for 3 patients and as monotherapy for 9 patients. 2-year OS and PFS rate was 50.1% (95% CI 38.6%-60.5%) and 38.5% (95% CI 27.9%-49.0%). On MVA, > 6 cycles of MTX was associated with superior OS, PFS, and LC. For patients receiving any chemotherapy, addition of R was associated with inferior OS while ITc was associated with improved OS, PFS, and LC (Table). There was no OS association on MVA with TMZ, GTR, consolidation WBRT, or size or number of initial lesions (p>0.05). Conclusions: Completion of induction HD-MTX and use of ITc was associated with better outcomes in this population. Incorporation of R into 1st line therapy was associated with worse OS. Survival remained poor throughout the study period, underscoring importance of further innovation. [Table: see text]