Wang Liang, Guan Wenxue, Peng Xiaoyan
Department of Hematology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Front Oncol. 2021 Apr 23;11:676792. doi: 10.3389/fonc.2021.676792. eCollection 2021.
Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy, and standard treatment approaches have not been defined yet. Bruton tyrosine kinase inhibitors are found to be effective in the treatment of primary central nervous system diffuse large B cell lymphoma. Herein, we retrospectively reported the efficacy and safety profiles of bruton tyrosine kinase inhibitors in three consecutive patients with VRL. All three cases of VRL occurred in patients with pre-treated primary central nervous system lymphoma and the central nervous system was not involved at the time of VRL diagnosis. They were treated with zanubrutinib, a bruton tyrosine kinase inhibitor, at 160 mg twice daily orally. Rapid improvement of visual acuity and tumor control was achieved in all involved eyes of these 3 patients. Complete remission was confirmed by fundus photograph and optical coherence tomography, and the level of interleukin-10, a well-recognized biomarker for vitreoretinal lymphoma, decreased to normal in all patients. Zanubrutinib was well tolerated in all three patients, and only one adverse event of grade 3 hypertension occurred, which resolved after adjusting antihypertensive drugs. As of March 2021, these three patients have been treated with zanubrutinib for 9 months, 7 months, and 6 months, respectively, and all remained in complete remission. In conclusion, targeting bruton tyrosine kinase with zanubrutinib in vitreoretinal lymphoma is feasible and our findings can be a foundation for a paradigm shift in treatment options for this rare disease. A prospective phase 2 study evaluating the efficacy and safety of zanubrutinib in patients with vitreoretinal lymphoma is ongoing to validate our findings (ChiCTR2000037921).
玻璃体视网膜淋巴瘤（VRL）是一种罕见的眼内恶性肿瘤，目前尚未确定标准治疗方法。发现布鲁顿酪氨酸激酶抑制剂对原发性中枢神经系统弥漫性大B细胞淋巴瘤有效。在此，我们回顾性报告了连续3例VRL患者使用布鲁顿酪氨酸激酶抑制剂的疗效和安全性。所有3例VRL均发生在先前接受过治疗的原发性中枢神经系统淋巴瘤患者中，在VRL诊断时中枢神经系统未受累。他们接受了布鲁顿酪氨酸激酶抑制剂泽布替尼治疗，口服剂量为每日两次，每次160mg。这3例患者所有受累眼的视力均迅速改善，肿瘤得到控制。通过眼底照片和光学相干断层扫描确认完全缓解，所有患者中公认的玻璃体视网膜淋巴瘤生物标志物白细胞介素-10水平降至正常。3例患者对泽布替尼耐受性良好，仅发生1例3级高血压不良事件，调整降压药物后缓解。截至2021年3月，这3例患者分别接受泽布替尼治疗9个月、7个月和6个月，均保持完全缓解。总之，在玻璃体视网膜淋巴瘤中用泽布替尼靶向布鲁顿酪氨酸激酶是可行的，我们的发现可为这种罕见疾病的治疗选择范式转变奠定基础。一项评估泽布替尼对玻璃体视网膜淋巴瘤患者疗效和安全性的前瞻性2期研究正在进行，以验证我们的发现（ChiCTR2000037921）。
