Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19
Antibody Response in Immunocompromised Patients With Hematologic Cancers Who Received a 3-Dose mRNA-1273 Vaccination Schedule for COVID-19
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DOI：
10.1001/jamaoncol.2022.3227
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发表时间：
2022-08-11
期刊：
影响因子：
28.4
通讯作者：
Nijhof, Inger S.
中科院分区：
文献类型：
--
作者：
Haggenburg, Sabine;Hofsink, Quincy;Nijhof, Inger S.
为免疫低下的血液病患者提供第三剂新冠肺炎疫苗已经成为一种常见的做法，但证实这一点的数据很少。目的评估第三次接种mRNA1273是否与免疫低下的血液病患者中和抗体浓度的增加有关，这些抗体浓度与标准的两剂mRNA1273接种方案后的健康人水平相当。参与者这项前瞻性观察队列研究是在荷兰的4所大学医院进行的，包括584名跨越血液病谱系的可评估患者和44名随机选择的年龄匹配的没有恶性或免疫缺陷合并症的成年人。在完成标准的2剂mRNA-1273疫苗接种计划5个月后，再接种一次mRNA-1273疫苗。主要结果和测量第三次mRNA-1273疫苗接种前和接种后4周的血清抗S_1亚单位(S1)抗体，以及野生型、Delta、结果在这组584例免疫功能低下的血液病患者中(平均年龄60[11.2]岁；216名(37.0%)妇女)，第三次接种mRNA1273疫苗后，S1-Ig G浓度的中位数与两剂mRNA1273方案后健康人获得的浓度相当。在第三次接种后，免疫系统恢复的患者的S1-Ig G浓度升高最为明显，但在持续免疫缺陷的患者中也观察到了有效的反应。具体地说，骨髓癌或多发性骨髓瘤患者以及自体或异基因造血细胞移植(HCT)的受者在两剂疗程后达到与健康人相似的S1-Ig G中值。接受抗CD20治疗的患者或在完成抗CD20治疗后不久，接受CD19指导的嵌合抗原受体T细胞治疗的患者，以及接受伊布鲁替尼的慢性淋巴细胞白血病患者，对第三次疫苗接种反应较差或无反应。在第二次和第三次接种之间接受细胞治疗的27名患者中，S1抗体被保留，但第三次mRNA1273接种与除接受自体HCT的多发性骨髓瘤患者外，没有显著增加的S1-IgG浓度相关。第三次接种与显著提高每个抗体的中和能力有关。结论和这项队列研究的相关结果支持，免疫功能低下的血液病患者的主要计划应该补充第三次延迟接种。B细胞淋巴瘤患者和异基因HCT接受者需要在治疗或移植后重新接种疫苗。
IMPORTANCE It has become common practice to offer immunocompromised patients with hematologic cancers a third COVID-19 vaccination dose, but data substantiating this are scarce.OBJECTIVE To assess whether a third mRNA-1273 vaccination is associated with increased neutralizing antibody concentrations in immunocompromised patients with hematologic cancers comparable to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule.DESIGN, SETTING, AND PARTICIPANTS This prospective observational cohort study was conducted at 4 university hospitals in the Netherlands and included 584 evaluable patients spanning the spectrum of hematologic cancers and 44 randomly selected age-matched adults without malignant or immunodeficient comorbidities.EXPOSURES One additional mRNA-1273 vaccination 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule.MAIN OUTCOMES AND MEASURES Serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after a third mRNA-1273 vaccination, and antibody neutralization capacity of wild-type, Delta, and Omicron variants in a subgroup of patients.RESULTS In this cohort of 584 immunocompromised patients with hematologic cancers (mean [SD] age, 60 [11.2] years; 216 [37.0%] women), a third mRNA-1273 vaccination was associated with median S1-IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1-IgG concentration after the third vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid cancers or multiple myeloma and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1-IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients receiving or shortly after completing anti-CD20 therapy, CD19-directed chimeric antigen receptor T-cell therapy recipients, and patients with chronic lymphocytic leukemia receiving ibrutinib were less responsive or unresponsive to the third vaccination. In the 27 patients who received cell therapy between the second and third vaccination, S1 antibodies were preserved, but a third mRNA-1273 vaccination was not associated with significantly enhanced S1-IgG concentrations except for patients with multiplemyeloma receiving autologous HCT. A third vaccination was associated with significantly improved neutralization capacity per antibody.CONCLUSIONS AND RELEVANCE Results of this cohort study support that the primary schedule for immunocompromised patients with hematologic cancers should be supplemented with a delayed third vaccination. Patients with B-cell lymphoma and allogeneic HCT recipients need to be revaccinated after treatment or transplantation.