Xing Limin, Wang Yihao, Liu Hui, Gao Shan, Shao Qing, Yue Lanzhu, Liu Zhaoyun, Wang Huaquan, Shao Zonghong, Fu Rong
Department of Hematology, General Hospital, Tianjin Medical University, Tianjin, China.
Front Oncol. 2021 Dec 23;11:798352. doi: 10.3389/fonc.2021.798352. eCollection 2021.
Chimeric antigen receptor T (CAR-T) cells show good efficacy in the treatment of relapsed and refractory B-cell tumors, such as acute B-cell leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The main toxicities of CAR-T include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia, and severe infection. It is still very difficult for CAR-T to kill tumor cells to the maximum extent and avoid damaging normal organs. Here, we report a case of DLBCL with persistent grade 4 thrombocytopenia and severe platelet transfusion dependence treated with CD19 CAR-T cells. We used sirolimus to inhibit the sustained activation of CAR-T cells and restore normal bone marrow hematopoiesis and peripheral blood cells. Moreover, sirolimus treatment did not affect the short-term efficacy of CAR-T cells, and DLBCL was in complete remission at the end of follow-up. In conclusion, sirolimus can represent a new strategy for the management of CAR-T cell therapy-related toxicity, including but not limited to hematotoxicity. However, further controlled clinical studies are required to confirm these findings.
嵌合抗原受体T(CAR-T)细胞在治疗复发难治性B细胞肿瘤方面显示出良好疗效,如急性B细胞白血病(ALL)和弥漫性大B细胞淋巴瘤(DLBCL)。CAR-T的主要毒性包括细胞因子释放综合征、免疫效应细胞相关神经毒性综合征、血细胞减少和严重感染。CAR-T要最大程度地杀死肿瘤细胞并避免损害正常器官仍然非常困难。在此,我们报告1例接受CD19 CAR-T细胞治疗的DLBCL患者,该患者持续存在4级血小板减少症且严重依赖血小板输血。我们使用西罗莫司抑制CAR-T细胞的持续活化,并恢复正常的骨髓造血和外周血细胞。此外,西罗莫司治疗不影响CAR-T细胞的短期疗效,随访结束时DLBCL完全缓解。总之,西罗莫司可代表一种管理CAR-T细胞治疗相关毒性的新策略,包括但不限于血液毒性。然而,需要进一步的对照临床研究来证实这些发现。