Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p = .0002 for both). Anti-spike IgG correlated with lymphocyte count (r = .63; p = .002), and time from treatment (r = .56; p = .007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p = .03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p = .0008) and HC (p < .0001). Anti-spike IgG correlated with neutralization of the delta variant (r = .62, p < .0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p < .0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p = .004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant.

中文翻译：

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用 BNT162b2 免疫治疗的惰性淋巴瘤患者对 SARS-CoV-2 变体的抗尖峰中和 IgG 减少，但保留了抗原特异性 T 细胞反应

接受反复或持续 B 细胞抑制的惰性淋巴瘤患者有患重症 COVID-19 的风险。患者和健康对照（HC；N  = 13）接受了两剂 BNT162b2：滤泡性淋巴瘤（FL；N  = 35），未接受治疗（TN；N  = 11）或接受免疫化疗（ICT；N  = 23）和瓦尔登斯特伦巨球蛋白血症（WM；N  = 37）包括 TN（N  = 9）、ICT（N  = 14）或接受布鲁顿氏酪氨酸激酶抑制剂治疗（BTKi；N = 12). 除活病毒中和外，还通过高灵敏度流式细胞术测定确定了抗刺突免疫球蛋白 G (IgG)。通过在 T 细胞上共表达 CD69/CD137 和 CD25/CD134 来鉴定抗原特异性 T 细胞。 评估了一个亚组 ( N = 29) 的第三次 mRNA 疫苗反应，包括 omicron 中和。在第二次 BNT162b2 后一个月，FL ICT 患者 (9977) 的中位抗尖峰 IgG 平均荧光强度 (MFI) 比 TN (245 898) 和 HC (228 255，两者p  = .0002) 低 25 倍。抗尖峰 IgG 与淋巴细胞计数 ( r  = .63；p  = .002) 和距治疗时间 ( r  = .56；p = .007)，在单变量分析中，但在多变量分析中仅使用淋巴细胞计数 ( p  = .03)。在 WM 队列中，与 TN (220 645， p  = .0008) 和 HC ( p  < .0001)相比，BTKi 患者 (39 039) 的中位抗尖峰 IgG MFI 有所降低。抗尖峰 IgG 与 delta 变体的中和相关（r  = .62，p  < .0001）。对于早期进化枝和三角洲，WM BTKi (0) 的中和效价中值低于 HC (40，p  < .0001)。所有队列都有功能性 T 细胞反应。从第二剂到第三剂，抗尖峰 IgG 的中值降低了 4 倍（p =.004）。在第三次疫苗接种后评估的 29 名最初反应较差的人中，只有 5 名表现出血清转化和中和活性的改善，包括对 omicron 变体的中和活性。