Relapses and outcomes of systemic chemo-free therapies combined with intravitreous methotrexate in isolated primary vitreoretinal lymphoma: an analysis based on two prospective cohort studies

The definitive therapeutic paradigm for primary vitreoretinal lymphoma (PVRL) remains controversial, with ongoing debates surrounding the comparative efficacy of localized ocular therapy, high-dose systemic chemotherapy, and combined-modality approaches. The benefit of systemic administration of methotrexate is unambiguous and severe adverse events related to intense chemotherapy are reported. Immunomodulators such as lenalidomide and Bruton's tyrosine kinase (BTK) inhibitors, like zanubrutinib, have not been explored for their safety and efficacy as first-line treatments for PVRL. This study aimed to analyze the safety and efficacy of chemo-free combination regimens in newly diagnosed PVRL patients. In our study, systemic chemo-free regimens were administrated as induction therapy, including the ZR regimen (zanubrutinib and rituximab), and the R2 regimen (lenalidomide and rituximab). Of the 44 patients, 41 (93.2%) achieved complete remission following induction therapy. No severe systemic adverse events were observed. After a median follow-up of 25.1 months, 17 patients (38.6%) suffered relapses, including one intraocular relapse and 17 brain relapses. By the final follow-up, 5 patients (11.4%) had died from disease progression. The median PFS and OS were 22.1 and 71.5 months, respectively. The ZR regimen demonstrated a longer PFS compared to the R2 regimen (10.9 months vs. not reached; log-rank test, P = 0.00044), positioning it as a promising treatment option for PVRL patients.