Long‐term outcomes of combined intravitreal methotrexate and systemic high‐dose methotrexate therapy in vitreoretinal lymphoma

Objective The optimal treatment for vitreoretinal lymphoma (VRL) remains a challenge, as central nervous system (CNS) relapse occurs frequently, leading to the worst impact on survival. We previously proposed combined intravitreal methotrexate and systemic high‐dose methotrexate therapy for this disease. This study aimed to report the long‐term outcomes of patients with VRL using this combination treatment. Methods We conducted a retrospective cohort study on patients with VRL at a tertiary referral center between 2003 and 2018. Results Thirty‐two patients were included, of whom 23 had primary VRL (PVRL) and nine had concurrent intraocular and CNS diseases. The treatment was well tolerated. Twenty‐six (81.3%) patients achieved complete response (CR). After a median follow‐up time of 103.5 months, the 5‐year survival rate was 73.3%, whereas the 5‐year progression‐free survival (PFS) rate was 29.9%. Twenty‐four (75%) patients relapsed, including 12 with isolated intraocular relapses at first relapse and a total of 17 with CNS/systemic relapses. The development of CNS/systemic relapse negatively affected survival, but intraocular relapse did not. The median CNS/systemic PFS was 69.5 months, but the risk of CNS/systemic relapse increased steadily with a cumulative incidence rate at 2, 5, and 10 years being 22.6%, 44.2%, and 65%, respectively. Multivariate analysis identified concurrent CNS disease at diagnosis as the only poor‐risk factor for CNS/systemic relapse. Conclusions This study confirms good efficacy and acceptable toxicities of the combination approach. However, incorporation of further intensive consolidation strategies into the treatment protocol to effectively prevent subsequent CNS/systemic relapse deserves to be considered. Our study showed the long‐term outcomes regarding the combined intravitreal MTX and systemic HDMTX therapy in patients with vitreoretinal lymphoma (VRL). This combination approach induced a high survival rate with acceptable toxicities. Nevertheless, more than half of patients experienced CNS/systemic relapse, accounting for the main cause of death. Incorporation of more intensive consolidation strategies into the treatment protocol deserves to be considered, especially for patients with concurrent CNS disease at diagnosis.