Humoral Responses Against SARS-CoV-2 and Variants of Concern After mRNA Vaccines in Patients With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

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
Source: DOI: 10.1200/JCO.22.00088 Journal of Clinical Oncology 40, no. 26
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Nice study from Emory quantifying the increased risk of infection in this vulnerable group.  These patients should remain vigilant in today’s environment and be considered for pre-exposure prophylaxis where available, in addition to staying up to date with vaccinations and follow-up boosters.   Even in untreated patients, titers were 11-fold lower than healthy vaccinees, confirming the disease causes an inherent immunodeficiency to COVID19.


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).


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.


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.


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

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