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利妥昔单抗治疗后出现体液免疫功能障碍的 B 细胞非霍奇金淋巴瘤患者使用 20%皮下免疫球蛋白替代疗法。

The Use of 20% Subcutaneous Immunoglobulin Replacement Therapy in Patients With B Cell Non-Hodgkin Lymphoma With Humoral Immune Dysfunction After Treatment With Rituximab.

机构信息

Division of Allergy, Immunology, and Rheumatology, Rochester Regional Health, Rochester, NY; Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY.

Division of Hematology and Oncology, Rochester Regional Health, Rochester, NY.

出版信息

Clin Lymphoma Myeloma Leuk. 2020 Sep;20(9):e590-e596. doi: 10.1016/j.clml.2020.04.006. Epub 2020 May 8.

Abstract

BACKGROUND

Rituximab is an anti-CD20 chimeric antibody used to treat autoimmune conditions and B cell neoplasms. We characterized immunoglobulin (Ig) levels and vaccine responses in rituximab-treated B cell non-Hodgkin lymphoma (NHL) patients. Patients with impaired vaccine responses were offered therapy with 20% subcutaneous (subq) Ig.

PATIENTS AND METHODS

Patients with a biopsy-proven diagnosis of B cell NHL who had received rituximab within the past 24 months were eligible for the study and underwent the following immune evaluation: serum IgG, IgM, IgA, IgE, T/B cell lymphocyte panel, and pre/post vaccine IgG titers to diphtheria, tetanus, and streptococcus pneumoniae. Patients were vaccinated with tetanus, diphtheria and pneumococcal polysaccharide vaccine. Patients with abnormal vaccine responses were offered prophylactic subq Ig for 52 weeks.

RESULTS

Fifteen patients with NHL were enrolled in the study. The median IgG was 628 mg/dL [interquartile range, 489-718 mg/dL]. Three (20%) of 15 patients responded to diphtheria vaccination, 1 (6.7%) of 15 responded to tetanus vaccination, and 3 (20%) of 15 responded to vaccination to streptococcus pneumoniae. Thirteen (86.7%) of 15 met criteria for humoral immunodeficiency. Ten patients received subq Ig, and experienced a significant increase in serum IgG (P = .008). There were no serious adverse events, and there was a decrease in nonneutropenic infections while on subq Ig therapy.

CONCLUSIONS

Patients with NHL treated with rituximab may have significant humoral immunodeficiency as defined by abnormal vaccine responses even in the setting of relatively normal IgG levels. For these patients, subq Ig replacement therapy is well-tolerated and efficacious in improving serum IgG, and may decrease reliance on antibiotics for the treatment of nonneutropenic infections.

摘要

背景

利妥昔单抗是一种抗 CD20 嵌合抗体,用于治疗自身免疫性疾病和 B 细胞肿瘤。我们对接受利妥昔单抗治疗的 B 细胞非霍奇金淋巴瘤(NHL)患者的免疫球蛋白(Ig)水平和疫苗反应进行了特征描述。对疫苗反应受损的患者,我们提供 20%皮下(subq)Ig 治疗。

患者和方法

本研究纳入了过去 24 个月内接受过利妥昔单抗治疗且经活检证实为 B 细胞 NHL 的患者,对其进行以下免疫评估:血清 IgG、IgM、IgA、IgE、T/B 细胞淋巴细胞谱以及白喉、破伤风和肺炎链球菌疫苗的预/后 IgG 滴度。患者接种破伤风、白喉和肺炎球菌多糖疫苗。对疫苗反应异常的患者,给予预防性 subq Ig 治疗 52 周。

结果

15 例 NHL 患者入组本研究。中位 IgG 为 628mg/dL[四分位距(IQR):489-718mg/dL]。15 例患者中,3 例(20%)对白喉疫苗有反应,1 例(6.7%)对破伤风疫苗有反应,3 例(20%)对肺炎链球菌疫苗有反应。15 例患者中有 13 例(86.7%)符合体液免疫缺陷标准。10 例患者接受了 subq Ig 治疗,血清 IgG 显著升高(P=0.008)。无严重不良事件,在接受 subq Ig 治疗期间,非中性粒细胞减少性感染减少。

结论

即使 IgG 水平相对正常,接受利妥昔单抗治疗的 NHL 患者也可能存在显著的体液免疫缺陷,表现为疫苗反应异常。对于这些患者,subq Ig 替代治疗耐受良好,可有效提高血清 IgG,减少对治疗非中性粒细胞减少性感染的抗生素的依赖。

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