血小板生成素受体激动剂用于 CAR-T 细胞治疗后持续性血小板减少的价值

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment landscape for various hematological malignancies.

However, it is associated with a range of hematologic complications, including severe and often prolonged thrombocytopenia. Currently, there are no known effective preventative or management measures against CAR-T-induced thrombocytopenia. At the University of Chicago Medical Center, thrombopoietin receptor agonists (TPO-RAs) eltrombopag and romiplostim have been utilized intermittently, per attending preference, in patients post CAR-T treatment presenting with prolonged thrombocytopenia (platelets <50 10 3 cells/ L for at least 14 days).

However, whether these treatments yield positive outcomes in this context remains uncertain.

This study aims to evaluate the efficacy and safety of TPO-RAs in patients with CAR-T-induced thrombocytopenia. The primary objective is to compare the incidence of platelet recovery (defined as two consecutive platelet counts of 50 10 3 cells/ L) in patients who received TPO-RAs versus those who did not for CAR-T-associated prolonged thrombocytopenia between January 1, 2018, and June 30, 2023. The secondary objectives include time to platelet recovery, incidence of clinically relevant bleed, hospital length of stay, incidence of adverse effects associated with TPO-RA administration, overall survival, and financial toxicity. This is a single-center, retrospective study conducted at the University of Chicago Medical Center. Eighty-five patients with prolonged, CAR-T-induced thrombocytopenia were enrolled in the study; 12 of these patients were managed with TPO-RA therapy while the remaining 73 received supportive care.

Statistical analysis was performed using STATA, incorporating the Chi-squared test for nominal data and the Wilcoxon Rank-sum test for continuous data. A P value of <. 05 was used to determine statistical significance. The incidence of platelet recovery was similar between the two groups; in the supportive care group, 53 patients (73%) experienced resolution of thrombocytopenia, compared to 9 patients (75%) in the TPO-RA treated group (P = 1. 0).

The median time to thrombocytopenia resolution was 56 days in the TPO-RA-treated group and 41 days in those not managed with TPO-RAs (P = . 14). The median time to TPO-RA initiation postinfusion was 45 days. There were no statistically significant differences in incidence of clinically relevant bleed or readmission within 1 year of CAR-T infusion between the two groups, but 25% of patients receiving TPO-RA therapy experienced associated arthralgia requiring treatment modification.

Additionally, the median cost of a course of eltrombopag was estimated at $86,921. 52 per patient at the reported average wholesale price. While TPO-RAs represent a theoretical therapeutic option for CAR-T patients based on their role in chemotherapy-induced thrombocytopenia, our study showed that their use did not provide significant clinical benefit compared to the supportive care approaches.

Therefore, without larger, randomized, prospective trials, we are unable to recommend TPO-RA use in this setting, given the current lack of demonstrated efficacy, potential adverse effects, and concerns regarding financial impact.