EFFICACY AND SAFETY OF BTK INHIBITORS IN VITREORETINAL LYMPHOMA: A SINGLE‐CENTER RETROSPECTIVE ANALYSIS OF 24 PATIENTS

Abstract

Purpose: Vitreoretinal lymphoma (VRL) is a rare subtype of lymphoma. The optimal treatment strategy is not yet defined. 60%–90% of VRL will progress to PCNSL. Therefore, central nervous system (CNS) prophylaxis for VRL patients is critical. Our previous studies have shown that BTK inhibitors monotherapy can replace repeated intravitreal injection of low-dose methotrexate, with rapid effect and a certain preventive value for the CNS. This study aimed to expand the sample size and extend the follow-up time to retrospectively analyze the efficacy and safety of BTK inhibitors in VRL. Method: A total of 24 VRL patients admitted to the Department of Hematology in Beijing Tongren Hospital from May 2020 to December 2022 were included. The clinical characteristics, treatment methods, treatment outcomes, survival status and treatment-related adverse reactions were retrospectively analyzed. Results: The median age was 62 years. There were 18 primary VRLs (PVRLs). The IL-10 in aqueous humor at baseline was significantly increased, and the IL-10/IL-6 ratio was greater than 1. There was no evidence of CNS involvement in 23 patients. All patients were treated with a BTK inhibitors (zanubrutinib 160 mg bid, or orelabrutinib 150 mg qd), and nine of them were also treated with intraocular injection of methotrexate. After 1 month of treatment, 21 patients had CR (87.5%) and 2 patients had PR (8.3%). The IL-10/IL-6 levels of aqueous humor were lower than 1 in all patients. The median duration of BTK inhibitors was 10 months. At a median follow-up of 17 months, 15 patients (62.5%) developed disease progression, including 11 with CNS infiltration and 4 with intraocular recurrence. The median PFS was 11.9 months, and the median OS was not reached. The 1-year PFS rate was 34% and the 1-year OS rate was 96%. The recurrence rate was 33.3% in the combined treatment group and 80.0% in the monotherapy group. Three patients died, all from CNS progression. BTK inhibitors were well tolerated, with grade 1-2 hypertension of 16.7%, grade 1 hypotension of 4.2%, grade 1 joint pain of 8.3%, grade 1 subcutaneous bleeding and ecchymosis of 25.0%. Four patients developed COVID-19 infection and BTK inhibitor medication was suspended. All patients had negative COVID-19 test within 2 weeks and did not develop significant pneumonia. Conclusion: BTK inhibitors showed rapid local control of VRL and were well tolerated. However, monotherapy with BTK inhibitors does not provide adequate central nervous system prophylaxis, and the combination of BTK inhibitors with other drugs, such as high-dose methotrexate, should be explored. The research was funded by: This work was supported by grants from the National Natural Science Foundation of China (grant No. 81873450, 82170181), Beijing Hospitals Authority Youth Programme (code: QML20200201), and Beijing Natural Science Foundation (No.7222027) to Liang Wang. Keywords: aggressive B-cell non-Hodgkin lymphoma, molecular targeted therapies No conflicts of interests pertinent to the abstract.