Author(s): Andres Chang, MD, PhD1,2;Akil Akhtar, PhD2;Susanne L. Linderman, PhD2;Lilin Lai, MD2,3,4;Victor M. Orellana-Noia, MD1;Rajesh Valanparambil, PhD2;Hasan Ahmed, MPH2,5;Veronika I. Zarnitsyna, PhD2,5;Ashley A. McCook-Veal, MPH6;Jeffrey M. Switchenko, PhD6;Jean L. Koff, MD1;Kristie A. Blum, MD1;Amy A. Ayers, MPH1,7;Colin B. O’Leary, MA1;Michael C. Churnetski, BSc1;Shahana Sulaiman, MD1;Melissa Kives, MPH1;Preston Sheng, BSc2;Carl W. Davis, MD, PhD2;Ajay K. Nooka, MD1;Rustom Antia, PhD2,5;Madhav V. Dhodapkar, MD1;Mehul S. Suthar, PhD2,3;Jonathon B. Cohen, MD1;and Rafi Ahmed, PhD2
PURPOSE
Patients with non-Hodgkin lymphoma including chronic lymphocytic leukemia (NHL/CLL) are at higher risk of severe SARS-CoV-2 infection. We investigated vaccine-induced antibody responses in patients with NHL/CLL against the original SARS-CoV-2 strain and variants of concern including B.1.167.2 (Delta) and B.1.1.529 (Omicron).
MATERIALS AND METHODS
Blood from 121 patients with NHL/CLL receiving two doses of vaccine were collected longitudinally. Antibody binding against the full-length spike protein, the receptor-binding, and N-terminal domains of the original strain and of variants was measured using a multiplex assay. Live-virus neutralization against Delta, Omicron, and the early WA1/2020 strains was measured using a focus reduction neutralization test. B cells were measured by flow cytometry. Correlation between vaccine response and clinical factors was determined.
RESULTS
Mean anti-SARS-CoV-2 spike immunoglobulin G–binding titers were 85-fold lower in patients with NHL/CLL compared with healthy controls, with seroconversion occurring in only 67% of patients. Neutralization titers were also lower and correlated with binding titers (P < .0001). Treatment with anti-CD20-directed therapies within 1 year resulted in 136-fold lower binding titers. Peripheral blood B-cell count also correlated with vaccine response. At 3 months from last anti-CD20-directed therapy, B-cell count ≥ 4.31/μL blood around the time of vaccination predicted response (OR 7.46, P = .04). Antibody responses also correlated with age. Importantly, neutralization titers against Delta and Omicron were reduced six- and 42-fold, respectively, with 67% of patients seropositive for WA1/2020 exhibiting seronegativity for Omicron.
CONCLUSION
Antibody binding and live-virus neutralization against SARS-CoV-2 and its variants of concern including Delta and Omicron were substantially lower in patients with NHL/CLL compared with healthy vaccinees. Anti-CD20-directed therapy < 1 year before vaccination and number of circulating B cells strongly predict vaccine response.
Author Affiliations
1Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA;2Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA;3Department of Pediatrics, Emory University Schools of Medicine, Atlanta, GA;4Yerkes National Primate Research Center, Atlanta, GA;5Department of Biology, Emory University, Atlanta, GA;6Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA;7Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
