Department of Internal Medicine, The University of Kansas Medical Center, Kansas City.
Department of Pharmacy, The University of Kansas Health System, Kansas City.
JAMA Oncol. 2022 Jul 1;8(7):1053-1058. doi: 10.1001/jamaoncol.2022.0752.
The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes.
To evaluate anti-SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT).
DESIGN, SETTING, AND PARTICIPANTS: In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose.
Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines.
Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines.
This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]).
In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.
重要性：癌症患者在接受治疗或接受干细胞移植期间 COVID-19 疫苗的抗体反应持久性尚不清楚，且可能与感染结局相关。
目的：评估癌症患者在接受治疗或接受干细胞移植（SCT）期间，接种 COVID-19 疫苗后 6 个月内抗 SARS-CoV-2 刺突蛋白受体结合域（anti-RBD）和中和抗体（nAb）的纵向反应。
设计、地点和参与者：这是一项在堪萨斯城堪萨斯大学癌症中心进行的前瞻性、观察性、纵向横断面研究，共纳入 453 名癌症患者，这些患者正在接受治疗或接受 SCT。在 433 名患者接受信使 RNA（mRNA）疫苗（BNT162b2 或 mRNA-1273）之前、第一剂 mRNA 疫苗后、第二剂 mRNA 疫苗后 1 个月、3 个月和 6 个月时，采集了这些患者的血样。还在 17 名患者接受 JNJ-78436735 疫苗后 2、4 和 7 个月时采集了这些患者的血样。对于接受第三剂 mRNA 疫苗的患者，在第三剂疫苗接种后 30 天采集血样。
干预措施：采集血样和 BNT162b2、mRNA-1273 或 JNJ-78436735 疫苗。
主要结局和措施：anti-RBD 的几何平均滴度（GMT）；分析人口统计学、疾病和治疗变量的 GMT 比值；anti-RBD 抗体中和百分比；以及 COVID-19 疫苗的 anti-RBD 和 nAb 反应之间的相关性。
结果：这项研究共纳入了 453 名患者（平均年龄[标准差]，60.4[13，1]岁；253[56%]为女性）。在 450 名患者中，273 名（61%）接受了 BNT162b2 疫苗（辉瑞），160 名（36%）接受了 mRNA-1273 疫苗（莫德纳），17 名（4%）接受了 JNJ-7846735 疫苗（强生）。所有患者接种疫苗前的 anti-RBD GMT 为 1.70（95%CI，1.04-2.85），第一剂疫苗后为 18.65（95%CI，10.19-34.11），第二剂疫苗后 1 个月为 470.38（95%CI，322.07-686.99），第二剂疫苗后 3 个月为 425.80（95%CI，322.24-562.64），第二剂疫苗后 6 个月为 447.23（95%CI，258.53-773.66），第三剂疫苗后为 9224.85（95%CI，2423.92-35107.55）。第二剂疫苗接种后 1 个月，252 名患者中有 203 名（80%）达到了阈值中和（≥30%），第二剂疫苗接种后 3 个月，166 名患者中有 135 名（81%）达到了阈值中和。anti-RBD 和 nAb 高度相关（Spearman 相关系数，0.93[0.92-0.94]；P < .001）。第二剂疫苗接种后 3 个月，男性患者的 anti-RBD 滴度低于女性患者（GMT 比值，0.52[95%CI，0.34-0.81]），65 岁以上的患者低于 50 岁以下的患者（GMT 比值，0.38[95%CI，0.25-0.57]），血液系统恶性肿瘤患者低于实体肿瘤患者（GMT 比值，0.40[95%CI，0.20-0.81]）。
结论和相关性：在这项横断面研究中，接种 2 剂 mRNA 疫苗后，anti-RBD 滴度在 1 个月时达到峰值，并在接下来的 6 个月内保持稳定。65 岁以上的患者、男性患者和血液系统恶性肿瘤患者的抗体滴度较低。与初始疫苗接种相比，第三剂疫苗接种后滴度增加了 20 倍，提示癌症患者的 B 细胞记忆反应活跃。
