BACKGROUND CD19-targeted chimeric antigen receptor T-cell therapy (CAR-T therapy) has revolutionized the treatment of hematologic malignancies. As these cells target CD19+ receptors on B cells, there is the potential for B-cell aplasia and hypogammaglobulinemia. Data on the degree and clinical significance of hypogammaglobulinemia are sparse. OBJECTIVES We sought to evaluate hypogammaglobulinemia after CD19-targeted CAR-T therapy and risk factors for hypogammaglobulinemia, infections, and mortality. METHODS We performed a retrospective evaluation of 579 patients receiving CD19-directed CAR-T therapy and evaluated demographics, hypogammaglobulinemia (IgG ≤600 mg/dL), infections prior to and after CAR-T therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality. RESULTS Patients had a mean age of 64 years and 64% were male. Prior to CAR-T therapy, 60% of patients had hypogammaglobulinemia, which increased to 91% post-CAR-T therapy. Mean IgG levels decreased from pre- to post-CAR-T therapy levels (587 to 362 mg/dL; P < .0001). Thirty-seven percent of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia prior to CAR-T therapy was associated with worsening hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia post CAR-T therapy was associated with an increased risk of serious infection following CAR-T therapy (incidence rate ratio: 2.7; 95% CI: 1.5-5.2; P = .002). Risk factors for mortality included mild hypogammaglobulinemia (400 mg/dL < IgG ≤ 600 mg/dL), infections ≤100 days post-CAR-T therapy, and hospitalizations for infections. Immunoglobulin replacement was associated with a decreased risk of mortality. CONCLUSIONS We identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia before CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia after CAR-T therapy, which was associated with an increased risk of serious infection and mortality post CAR-T therapy. Increased immunological monitoring is needed to identify high-risk patients who may benefit from interventions to decrease morbidity and mortality.

中文翻译：

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CD19 + 靶向嵌合抗原受体 （CAR） T 细胞疗法与低丙种球蛋白血症、感染和死亡率的相关性。


背景 靶向 CD19 的嵌合抗原受体 T 细胞疗法 （CAR-T 疗法） 彻底改变了血液系统恶性肿瘤的治疗。由于这些细胞靶向 B 细胞上的 CD19+ 受体，因此可能存在 B 细胞再生障碍和低丙种球蛋白血症。关于低丙种球蛋白血症的程度和临床意义的数据很少。目的 我们试图评估 CD19 靶向 CAR-T 治疗后低丙种球蛋白血症以及低丙种球蛋白血症、感染和死亡率的危险因素。方法 我们对 579 例接受 CD19 定向 CAR-T 治疗的患者进行了回顾性评估，并评估了人口统计学、低丙种球蛋白血症 （IgG ≤600 mg/dL）、CAR-T 治疗前后的感染以及低丙种球蛋白血症、感染、住院和死亡率的危险因素。结果 患者平均年龄为 64 岁，其中 64% 为男性。在 CAR-T 治疗之前，60% 的患者患有低丙种球蛋白血症，CAR-T 治疗后增加到 91%。平均 IgG 水平从 CAR-T 治疗前到治疗后水平下降（587 至 362 mg/dL;P < .0001）.37% 的患者在 CAR-T 治疗后发生严重感染。CAR-T 治疗前的低丙种球蛋白血症与 CAR-T 治疗后低丙种球蛋白血症恶化相关。CAR-T 治疗后低丙种球蛋白血症与 CAR-T 治疗后严重感染风险增加相关（发病率比：2.7;95% CI：1.5-5.2;P = .002）。死亡的危险因素包括轻度低丙种球蛋白血症 （400 mg/dL < IgG ≤ 600 mg/dL）、感染≤CAR-T 治疗后 100 天）和感染住院。免疫球蛋白替代治疗与死亡风险降低相关。 结论 我们确定了 CAR-T 治疗后 ∼90% 的低丙种球蛋白血症患者。CAR-T 治疗前的低丙种球蛋白血症强烈预测 CAR-T 治疗后低丙种球蛋白血症恶化，这与 CAR-T 治疗后严重感染和死亡的风险增加有关。需要加强免疫学监测，以识别可能受益于降低发病率和死亡率的干预措施的高危患者。