Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q1, Q3)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q1, Q3)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ2=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.
目的： 探讨复发难治多发性骨髓瘤（RRMM）患者接受B细胞成熟抗原（BCMA）嵌合抗原受体T细胞（CAR-T）治疗后血细胞减少的特征及对预后的影响。 方法： 回顾性收集2017年4月至2023年3月南京医科大学第一附属医院接受BCMA CAR-T治疗的36例RRMM患者的临床资料，其中男17例，女19例，年龄［M（Q1，Q3）］为62（53，67）岁。随访截至2023年8月31日，随访时间［M（Q1，Q3）］为33（10，30）个月。分析所有患者清除淋巴细胞前、CAR-T回输后不同时间点的血细胞减少特征。采用Kaplan-Meier法绘制生存曲线，比较不同临床特征患者无进展生存时间（PFS）及总生存时间（OS）的差异；采用单细胞测序分析其中3例患者CAR-T治疗后造血干细胞变化特征。 结果： 36例RRMM患者接受BCMA CAR-T治疗后血细胞减少发生率达100%。中性粒细胞减少发生率在回输后第7天［全部等级中性粒细胞减少占61.1%（22/36），≥3级中性粒细胞减少占33.3%（12/36）］和第28天［全部等级中性粒细胞减少占67.9%（19/28），≥3级中性粒细胞减少占28.6%（8/28）］呈现峰值，呈双相型变化（P<0.001）。淋巴细胞减少在回输当天即达高峰［全部等级淋巴细胞减少占97.2%（35/36），≥3级淋巴细胞减少占80.6%（29/36）］（P<0.001）。全部等级血小板减少和重度血小板减少（≥3级）的发生率在回输后第14天达到高峰，分别为69.4%（25/36）、30.6%（11/36），且持续时间长（P<0.001）；回输后12个月仍有40%（8/20）患者发生血小板减少。贫血发生率在回输后第7、14天达到高峰，为100%（36/36），恢复缓慢（P<0.001）；回输后12个月仍有50%（10/20）患者发生贫血。Kaplan-Meier生存分析显示，血小板减少<3级患者的OS为未达到，血小板减少≥3级患者的OS缩短［17（95%CI：2~32）个月，χ2=4.154，P=0.042］，预后较差；而其他血细胞减少和生存的关系差异均无统计学意义（均P>0.05）。骨髓单细胞测序分析发现CAR-T回输后造血干细胞增殖减少、凋亡增加、细胞周期受阻。 结论： 所有患者在接受BCMA CAR-T输注后均出现不同程度血细胞减少，血小板减少≥3级患者的OS缩短，预后较差。.