BMT Unit, Tel Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ann Hematol. 2022 Aug;101(8):1769-1776. doi: 10.1007/s00277-022-04889-6. Epub 2022 Jun 22.
Anti CD-19 chimeric antigen receptor T (CAR-T) cells demonstrate effective early anti-tumor response; however, impaired hematopoietic recovery is observed in about 30% of patients with prolonged cytopenia appearing as an unmet need for optimal treatment. All adult patients given commercially available anti CD-19 CAR-T for diffuse large B cell lymphoma (DLBCL) were screened at 21-28 days after CAR-T infusion for cytopenia. In case of severe persistent cytopenia, patients were given TPO receptor agonists. Initial dose of eltrombopag was 50 mg/day and gradually increased to a maximal dose of 150 mg/day. Romiplostim was given as subcutaneous injection once a week for 2 doses (125 mcg). Response was defined as transfusion independency along with resolution of severe neutropenia (ANC > 500 /microL) and/or platelets > 20,000/microL for three consecutive values on different days. TPO receptor agonists were tapered down when response was met. From May 2019 to December 2021, 93 patients were eligible (74%, tisagenlecleucel and 26%, axicabtagene ciloleucel). The median age was 69 (range, 19-85) years. Six patients (6.5%) (tisagenlecleucel, n = 4 or axicabtagene ciloleucel, n = 2) demonstrated prolonged severe cytopenia and were treated with TPO receptor agonists (eltrombopag, n = 4; romiplastim, n = 1, both drugs, n = 1). Median time from CAR-T infusion to initiation of TPO receptor agonist was 43 (range, 21-55) days. All patients were transfusion-dependent and were given daily GCSF prior to TPO receptor agonist administration. Response to TPO receptor agonists was seen in all 6 patients. Median time from TPO receptor agonist initiation to resolution of cytopenia was 22 (range, 8-124) days for Hb, 27 (range, 6-38) days for platelets, and 29 (range, 7-61) days for neutrophils. A complete resolution of all blood counts (ANC > 500 /microL and platelets > 20,000/microL and hemoglobin > 8 gr/dL) was seen in 5/6 patients. No toxicity was observed during the therapy course. This paper supports further investigation of TPO receptor agonists in the treatment of persistent cytopenia following CAR-T cell therapy.
抗 CD-19 嵌合抗原受体 T（CAR-T）细胞表现出有效的早期抗肿瘤反应；然而，约 30%的接受商业化抗 CD-19 CAR-T 治疗弥漫性大 B 细胞淋巴瘤（DLBCL）的成年患者出现长期血细胞减少，这是未满足的最佳治疗需求。在 CAR-T 输注后 21-28 天，对所有接受抗 CD-19 CAR-T 治疗的弥漫性大 B 细胞淋巴瘤（DLBCL）成年患者进行血细胞减少筛查。在出现严重持续性血细胞减少的情况下，给予患者血小板生成素受体激动剂。艾曲泊帕的初始剂量为 50mg/天，逐渐增加至 150mg/天的最大剂量。罗米司亭每周皮下注射一次，共 2 次（125 mcg）。反应定义为连续 3 天不同日期输注独立性以及严重中性粒细胞减少症（ANC>500 /microL）和/或血小板>20,000/microL的缓解。当达到反应时，逐渐减少血小板生成素受体激动剂的剂量。从 2019 年 5 月至 2021 年 12 月，93 名患者符合条件（74%，tisagenlecleucel 和 26%，axicabtagene ciloleucel）。中位年龄为 69 岁（范围，19-85 岁）。6 名患者（6.5%）（tisagenlecleucel，n=4 或 axicabtagene ciloleucel，n=2）出现持续性严重血细胞减少，并接受血小板生成素受体激动剂（艾曲泊帕，n=4；罗米司亭，n=1，两种药物，n=1）治疗。从 CAR-T 输注到开始使用血小板生成素受体激动剂的中位时间为 43 天（范围，21-55 天）。所有患者在接受血小板生成素受体激动剂治疗前均依赖输血，并每日给予 G-CSF。所有 6 名患者对血小板生成素受体激动剂均有反应。从开始使用血小板生成素受体激动剂到血细胞减少缓解的中位时间为血红蛋白 22 天（范围，8-124 天），血小板 27 天（范围，6-38 天），中性粒细胞 29 天（范围，7-61 天）。5/6 名患者的所有血液计数（ANC>500 /microL 和血小板>20,000/microL 和血红蛋白>8 gr/dL）完全缓解。在治疗过程中未观察到毒性。本文支持进一步研究血小板生成素受体激动剂在 CAR-T 细胞治疗后持续性血细胞减少症中的治疗作用。
