Massachusetts General Hospital Cancer Center, Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
Dana-Farber Cancer Institute, Boston, MA.
J Clin Oncol. 2022 Jan 1;40(1):12-23. doi: 10.1200/JCO.21.01891. Epub 2021 Nov 9.
The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood.
We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti-SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison.
Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log geometric mean concentration [GMC] 2.9, log geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses ( < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type ( < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses ( = .002 for concentration, = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose).
Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.
患有癌症的患者接种 SARS-CoV-2 疫苗的免疫原性和反应原性尚不清楚。
我们对患有实体瘤或血液系统恶性肿瘤的成年人进行了一项前瞻性队列研究,以评估两剂 mRNA-1273、BNT162b2 或一剂 Ad26.COV2.S 接种后 7 天以上的抗 SARS-CoV-2 免疫球蛋白 A/M/G 刺突抗体、中和抗体以及反应原性。我们通过多变量回归分析来分析反应,并纳入了先前报告的 1638 名健康对照者的数据进行比较。
在 2021 年 4 月至 7 月期间,我们招募了 1001 名患者;其中 762 名符合分析条件(762 名可测量中和作用)。mRNA-1273 的免疫原性最强(几何平均浓度 [GMC] 2.9,几何平均中和滴度 [GMT] 2.3),其次是 BNT162b2(GMC 2.4;GMT 1.9)和 Ad26.COV2.S(GMC 1.5;GMT 1.4;<0.001)。Ad26.COV2.S 接种者中低中和作用(<恢复期滴度的 20%)的比例为 69.9%。在队列中,7.1%的患者既往感染过 COVID-19,与更高的反应相关(<0.001)。与可比的健康对照组相比,无论疫苗类型如何,癌症患者的抗体滴度和中和作用均较低(<0.001)。在过去 1 年内接受过化疗或正在接受皮质类固醇治疗与较低的抗体水平相关,而免疫检查点阻断与较高的中和作用相关。全身反应性因疫苗而异,并与免疫反应相关(浓度相关,=0.002;中和作用相关,=0.016)。在接受额外疫苗剂量的 32 名患者中,副作用与之前的剂量相似,其中 30 名患者的抗体滴度增加(额外剂量前的 GMC 为 1.05,剂量后为 3.17)。
癌症患者对 SARS-CoV-2 疫苗的免疫反应适度受损。这些数据表明,抗体检测可用于识别可能对额外疫苗剂量有效和合适的患者,尽管还需要更大规模的前瞻性研究。