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

• Published in: Journal of clinical oncology Vol. 40; no. 26; pp. 3020 - 3031
• Main Authors: Chang, Andres, Akhtar, Akil, Linderman, Susanne L, Lai, Lilin, Orellana-Noia, Victor M, Valanparambil, Rajesh, Ahmed, Hasan, Zarnitsyna, Veronika I, McCook-Veal, Ashley A, Switchenko, Jeffrey M, Koff, Jean L, Blum, Kristie A, Ayers, Amy A, O'Leary, Colin B, Churnetski, Michael C, Sulaiman, Shahana, Kives, Melissa, Sheng, Preston, Davis, Carl W, Nooka, Ajay K, Antia, Rustom, Dhodapkar, Madhav V, Suthar, Mehul S, Cohen, Jonathon B, Ahmed, Rafi
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 10.09.2022
• Subjects: COVID-19 - prevention & control; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Lymphoma, Non-Hodgkin - therapy; mRNA Vaccines; RAPID COMMUNICATIONS; SARS-CoV-2; Vaccines; Vaccines, Synthetic; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.22.00088

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 ( < .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, = .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.