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

Abstract

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 2 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 IgG was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by co-expression 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 (245898) and HC (228255, p=0.0002 for both). Anti-spike IgG correlated with lymphocyte count (r=0.63; p=0.002), and time from treatment, (r=0.56; p=0.007) on univariate analysis, but only with lymphocyte count on multivariate analysis (p=0.03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39039) was reduced compared to TN (220645, p=0.0008) and HC (p<0.0001). Anti-spike IgG correlated with neutralization of the delta variant (r=0.62, p<0.0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p<0.0001) 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=0.004). Only 5/29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant. This article is protected by copyright. All rights reserved.