Efficacy and safety of first-line combination therapy versus monotherapy for vitreoretinal lymphoma: A systematic review and meta-analysis

Abstract

Abstract Background Vitreoretinal lymphoma (VRL) is usually treated with a combo of intraocular methotrexate, high-dose intravenous methotrexate, and local radiotherapy as the first options. The effectiveness and safety of monotherapy such as BTK inhibitors, temozolomide, and pomalidomide for PVRL remain uncertain. Methods A systematic review and meta-analysis of clinical trial data and conference abstracts in VRL patients treated with first-line combination therapy and monotherapy were conducted through a search of PubMed, Embase, and Scopus databases until December 2022. A total of 17 studies comprising 278 patients were included, and survival data were extracted from 151 patients due to inconsistent units across studies. Results The combined treatment group used ioMTX + chemotherapy (in 3 studies), bilateral RT + chemotherapy (in 2 studies), ioMTX/IV HD-MTX based regimen (in 2 studies), ioMTX + chemotherapy + rdWBRT (in 2 studies), and ioMTX + lenalidomide/BTKi (in 2 studies). The monotherapy group used pomalidomide, temozolomide, and BTKi. The combination therapy had a higher overall response rate (ORR) and complete response rate (CRR) than monotherapy (ORR: 95% vs. 72%, CRR: 94% vs. 63%). Combination therapy also resulted in a longer median progression-free survival (33 months vs. 13 months, p = 0.0059). However, the combination therapy group had more severe side effects (grade 3/4 toxicity) than the monotherapy group (46% vs. 8%). Conclusion The study showed combination therapy had better OR and CR rates, longer survival, and more toxicity than monotherapy. While BTK inhibitors were well-tolerated, long-term effectiveness needs confirmation from prospective studies. Systematic review registration: CRD42023400305