Abstract：
Immune responses to primary COVID-19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016-004010-10). COVID-19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide-based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS-CoV-2 spike protein using the Abbott Architect and interferon-gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T-cell responses. Within the FL cohort, multivariable analysis identified low pre-treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T-cell responses, and bendamustine and high/intermediate FLIPI-2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID-19 vaccines in FL patients is influenced by multiple disease- and treatment-related factors, among which B-cell depletion showed differential effects on antibody and T-cell responses.
摘要：
作为一线治疗PETReA试验的一部分，在58例滤泡性淋巴瘤(FL)患者中调查了对初次COVID-19疫苗接种的免疫反应(EudraCT2016-004010-10)。COVID-19疫苗（BNT162b2或ChAdOx1）在利妥昔单抗（消耗B细胞）和苯达莫司汀（消耗CD4+T细胞）或环磷酰胺为基础的化疗的细胞减灭性治疗期间或之后。分别使用AbbottArchitect和干扰素-γELISpot测定法分析疫苗剂量1和2（V1，V2）后获得的血液样品中与SARS-CoV-2刺突蛋白反应的抗体和T细胞。与149名健康对照相比，FL患者表现出较低的抗体,但T细胞应答保留.在FL队列中，多变量分析确定低治疗前血清IgA水平和诱导或维持治疗期间的V2给药是较低抗体和较高T细胞反应的独立决定因素。苯达莫司汀和高/中FLIPI-2评分作为较低抗体反应的其他决定因素。确定了几种临床情景,其中基于预测变量的组合以>95%的置信度估计二分免疫应答。总之,FL患者中COVID-19疫苗的免疫原性受多种疾病和治疗相关因素的影响，其中B细胞耗竭对抗体和T细胞反应有不同的影响.
