Targeting Bruton’s tyrosine kinase in vitreoretinal lymphoma: an open-label, prospective, single-center, phase 2 study

Vitreoretinal lymphoma (VRL) is strongly linked to central nervous system (CNS) progression with no standard treatment approaches. Commonly used strategies include repeated intraocular injections of low-dose methotrexate or local radiotherapy, with great inconvenience, long-term side effects, and high risk of CNS relapse. In this study, we evaluated the efficacy and safety of bruton’s tyrosine kinase inhibitors (BTKi) in the treatment of VRL. This prospective single-center study enrolled patients with relapsed or newly diagnosed VRL between October 2020 and April 2022. Patients received BTKi monotherapy until disease progression or unacceptable toxicity. The primary endpoint was the disease control (DC) rate after one month of treatment; secondary endpoints include toxicity, overall survival (OS), and progression-free survival (PFS). Ten consecutive patients with VRL were enrolled into this study. After 1-month treatment, 9 patients (90%) achieved a DC, with 7 patients (70%) achieving a complete response (CR). With a median follow-up of 8.3 (2.5–21.4) months, 4 patients were confirmed to have disease progression, with a PFS of 1.2, 7.5, 9.1, and 11.6 months, respectively. The remaining 6 patients have durable control of disease and were still on treatment at time of the analysis. BTKi were well-tolerated and no patients discontinued the drug because of adverse events. In conclusion, targeting BTK in VRL is viable, and our findings could pave the way for a paradigm change in VRL therapy choices. Further large-scale studies, however, are required to give stronger evidence about the efficacy and safety. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-022-00354-2.