Natalia M Sutherland, Baijun Zhou, Lingxiao Zhang, Mei-Sing Ong, Joseph S Hong, Andrew Pak, Katherine J Liu, Matthew J Frigault, Marcela V Maus, Joshua A Hill, Kerry Reynolds, Jolan E Walter, Carlos A Camargo, Sara Barmettler
{"title":"CD19+靶向嵌合抗原受体（CAR）T细胞疗法与低丙种球蛋白血症、感染和死亡率的关系。","authors":"Natalia M Sutherland, Baijun Zhou, Lingxiao Zhang, Mei-Sing Ong, Joseph S Hong, Andrew Pak, Katherine J Liu, Matthew J Frigault, Marcela V Maus, Joshua A Hill, Kerry Reynolds, Jolan E Walter, Carlos A Camargo, Sara Barmettler","doi":"10.1016/j.jaci.2024.10.021","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To evaluate hypogammaglobulinemia after CD19-targeted CAR-T therapy and risk factors for hypogammaglobulinemia, infections, and mortality.</p><p><strong>Methods: </strong>We performed a retrospective evaluation of 579 patients receiving CD19-directed CAR-T therapy and evaluated demographics, hypogammaglobulinemia (immunoglobulin G [IgG]≤600mg/dL), infections pre- and post-CAR-T therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality.</p><p><strong>Results: </strong>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 (587 to 362 mg/dL; p<0.0001). 37% of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was associated with worsening hypogammaglobulinemia post-CAR-T therapy. Hypogammaglobulinemia post-CAR-T therapy was associated with an increased risk of serious infection post-CAR-T therapy (IRR=2.7; 95% CI=1.5-5.2; p=0.002). Risk factors for mortality included mild hypogammaglobulinemia (400mg/dL<IgG≤600mg/dL), infections ≤100 days post-CAR-T therapy, and hospitalizations for infections. Immunoglobulin replacement was associated with a decreased risk of mortality.</p><p><strong>Conclusions: </strong>We identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia post-CAR-T therapy, which was associated with an increased risk of serious infection and mortality post-CAR-T therapy. 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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.</p><p><strong>Objective: </strong>To evaluate hypogammaglobulinemia after CD19-targeted CAR-T therapy and risk factors for hypogammaglobulinemia, infections, and mortality.</p><p><strong>Methods: </strong>We performed a retrospective evaluation of 579 patients receiving CD19-directed CAR-T therapy and evaluated demographics, hypogammaglobulinemia (immunoglobulin G [IgG]≤600mg/dL), infections pre- and post-CAR-T therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality.</p><p><strong>Results: </strong>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 (587 to 362 mg/dL; p<0.0001). 37% of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was associated with worsening hypogammaglobulinemia post-CAR-T therapy. Hypogammaglobulinemia post-CAR-T therapy was associated with an increased risk of serious infection post-CAR-T therapy (IRR=2.7; 95% CI=1.5-5.2; p=0.002). Risk factors for mortality included mild hypogammaglobulinemia (400mg/dL<IgG≤600mg/dL), infections ≤100 days post-CAR-T therapy, and hospitalizations for infections. Immunoglobulin replacement was associated with a decreased risk of mortality.</p><p><strong>Conclusions: </strong>We identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia post-CAR-T therapy, which was associated with an increased risk of serious infection and mortality post-CAR-T therapy. 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引用次数: 0
摘要
背景：CD19 靶向嵌合抗原受体 T 细胞疗法（CAR-T疗法CD19靶向嵌合抗原受体T细胞疗法（CAR-T疗法）为血液恶性肿瘤的治疗带来了革命性的变化。由于这些细胞靶向 B 细胞上的 CD19+ 受体，因此有可能导致 B 细胞增生和低丙种球蛋白血症。有关低丙种球蛋白血症的程度和临床意义的数据很少：评估 CD19 靶向 CAR-T 治疗后的低丙种球蛋白血症以及低丙种球蛋白血症、感染和死亡率的风险因素：我们对579名接受CD19靶向CAR-T疗法的患者进行了回顾性评估，评估了人口统计学、低丙种球蛋白血症（免疫球蛋白G [IgG]≤600mg/dL）、CAR-T疗法前后的感染以及低丙种球蛋白血症、感染、住院和死亡率的风险因素：患者平均年龄为64岁，64%为男性。接受CAR-T治疗前，60%的患者患有低丙种球蛋白血症，接受CAR-T治疗后，这一比例上升至91%。平均 IgG 水平从 CAR-T 治疗前到治疗后有所下降（从 587 mg/dL 降至 362 mg/dL; p结论：我们发现 90% 的患者在接受 CAR-T 治疗后出现低丙种球蛋白血症。CAR-T治疗前的低丙种球蛋白血症可强烈预测CAR-T治疗后低丙种球蛋白血症的恶化，而低丙种球蛋白血症与CAR-T治疗后严重感染和死亡风险的增加有关。需要加强免疫监测，以识别可能受益于干预措施的高风险患者，从而降低发病率和死亡率。
Association of CD19+-Targeted Chimeric Antigen Receptor (CAR) T-cell Therapy with Hypogammaglobulinemia, Infection and Mortality.
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.
Objective: 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 (immunoglobulin G [IgG]≤600mg/dL), infections pre- and post-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 (587 to 362 mg/dL; p<0.0001). 37% of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was associated with worsening hypogammaglobulinemia post-CAR-T therapy. Hypogammaglobulinemia post-CAR-T therapy was associated with an increased risk of serious infection post-CAR-T therapy (IRR=2.7; 95% CI=1.5-5.2; p=0.002). Risk factors for mortality included mild hypogammaglobulinemia (400mg/dL
Conclusions: We identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia post-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.
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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