Poor neutralizing antibody responses in 106 patients with WM after vaccination against SARS-CoV-2: a prospective study

Maria Gavriatopoulou, Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Alexandros Briasoulis, Sentiljana Gumeni, Panagiotis Malandrakis, Despina Fotiou, Magdalini Migkou, Foteini Theodorakakou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Efstathios Kastritis, Ioannis P Trougakos, Meletios A Dimopoulos, Maria Gavriatopoulou, Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Alexandros Briasoulis, Sentiljana Gumeni, Panagiotis Malandrakis, Despina Fotiou, Magdalini Migkou, Foteini Theodorakakou, Evangelos Eleutherakis-Papaiakovou, Nikolaos Kanellias, Efstathios Kastritis, Ioannis P Trougakos, Meletios A Dimopoulos

Abstract

Immunocompromised patients with hematologic malignancies are more susceptible to COVID-19 and at higher risk of severe complications and worse outcomes compared with the general population. In this context, we evaluated the humoral response by determining the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenström macroglobulinemia (WM) after vaccination with the BNT162b2 or AZD1222 vaccine. A US Food and Drug Administration-approved enzyme-linked immunosorbent assay-based methodology was implemented to evaluate NAbs on the day of the first vaccine shot, as well as on days 22 and 50 afterward. A total of 106 patients with WM (43% men; median age, 73 years) and 212 healthy controls (46% men; median age, 66 years) who were vaccinated during the same period at the same center were enrolled in the study (which is registered at www.clinicaltrials.gov as #NCT04743388). Our data indicate that vaccination with either 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients with WM compared with controls on days 22 and 50 (P < .001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with either rituximab or Bruton's tyrosine kinase inhibitors was proven as an independent prognostic factor for suboptimal antibody response after vaccination. In conclusion, patients with WM have low humoral response after COVID-19 vaccination, which underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.

© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Kinetics of NAbs in patients with WM compared with controls after vaccination with 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine. On day 22, patients had lower NAb inhibition titers compared with controls (see text). Only 21 of 106 (19.8%) patients had NAb titers of equal or more than 50%. Similarly, patients had lower NAb inhibition titers compared with controls on day 50 (see text). Only 31 of 74 (42%) patients had NAb titers of equal or more than 50%.

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