Primary Vitreoretinal Lymphoma with or without Intracranial Involvement: A Single Center Experience

Introduction

Primary vitreoretinal lymphoma (PVRL) is a rare manifestation of primary central nervous system lymphoma, with most cases classified as diffuse large B-cell lymphoma (DLBCL). Local therapies aimed at restoration of vision and prevention of central nervous system dissemination typically have excellent response rates, but local recurrence and fatal brain relapse is common. With an estimated 50 new cases per year in the United States, epidemiological data and standardized treatment guidelines are lacking. Herein, we report outcomes of one of the largest single institutional populations of PVRL patients with or without brain involvement.

Methods/Materials

Patients with histologically confirmed PVRL (DLBCL), with or without brain involvement and diagnosed between 2016-2024 were included. Demographics, genomics, and treatment patterns were assessed. Differences in median or mean overall survival (OS) and relapse free survival (RFS) with 95% confidence interval (CI) based on treatment modality (local, systemic, local+systemic), brain involvement at diagnosis, and consolidative therapies was estimated by Kaplan-Meier methodology and compared by the Log-Rank test. P-value <0.05 was considered statistically significant.

Results

A total of 31 patients were diagnosed. Median age was 68 (50-85) years, 20 (64.5%) were female, and 18 (58%) were non-Hispanic white. There were 10 (32.2%) patients with at least one genomic alteration, with MYD88 reported in 5 (50.0%). There were 27 patients with available treatment data. Of these, 10 (37.0%) had unilateral disease, 10 (37.0%) had bilateral ocular involvement, and 7 (18.9%) had unilateral ocular and brain involvement. Upfront therapy included local therapy in 7 (18.9%), systemic therapy in 5 (18.5%), and systemic+local therapy in 15 (55.6%). Overall response rate (ORR) with local therapy was 85.7%, relapse rate was 47.8%, and 1 (14.7%) patient died. ORR with systemic therapy was 80%, relapse rate was 60%, and 40% died. ORR with local+systemic therapy was 80%, relapse rate was 53.3%, and 20% died. Of the 15 (55.6%) total relapses, 7 (46.7%) had brain dissemination; 6 (40.0%) had isolated ocular lymphoma at diagnosis, 8 (53.3%) had received systemic+local therapy, and 4 (26.7%) received systemic therapy only. Of the 12 (44.4%) with no relapse, all 12 (100%) had ocular disease only, 7 (53.8%) received local+systemic therapy, and 1 (8.3%) received systemic therapy. Median RFS and OS for all patients was 12.8 (95% CI 0.59, 64.99) months and 31.9 (95% CI 0.59, 101.85) months, respectively. Mean RFS for ocular only vs ocular+brain disease was 46.9 (95% CI 32.7, 61.2) vs 24.6 (95% CI 33.0, 58.9) (p=0.538) months, respectively, whereas mean OS was 60.1 (95% CI 48.8, 71.4) and 80.6 (95% CI 55.3, 105.9) (p=0.845) months, respectively. Mean RFS for local, systemic, and local+systemic was 35.7 (95% CI 24.0, 47.4) vs 18.2 (95% CI5.4, 31.0) vs 47.6 (95% CI 31.4, 63.8) (p=0.337) months, and OS was 57.6 (95% CI 39.0, 76.2), 53.7 (95% CI 31.4, 76.1), and 77.1 (95% CI 55.2, 98.9) (p=0.772) months, respectively. Receipt of autologous stem cell transplantation at any time during their disease course had RFS of 52.6 (95% CI 37.3, 67.9) vs 35.5 (95% CI 25.5, 45.5) (p=0.784) and OS of 82.4 (95% CI 60.3, 104.5) vs 54 (95% CI 40.3, 68.9) (p=0.387) months, respectively.

Conclusion

In one of the largest real-world studies of PVRL, patients with or without brain involvement had an ORR of 81.4%, but 55.6% relapsed and 22.2% died. Further studies are needed to assess the benefit of applying a local+systemic therapy approach including in those with localized disease to improve ocular morbidity and reduce ocular and brain relapse.