Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti‐spike neutralizing IgG to SARS‐CoV‐2 variants, but preserved antigen‐specific T cell responses

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.