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Evaluation of the Durability of the Immune Humoral Response to COVID-19 Vaccines in Patients With Cancer Undergoing Treatment or Who Received a Stem Cell Transplant

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant?

Findings  In this cross-sectional study of 453 patients with cancer undergoing treatment or who received a stem cell transplant, the geometric mean titers for the anti–SARS-CoV-2 spike protein receptor binding domain were 470.38 U/mL 1 month after the second dose of the vaccine, 447.23 U/mL 6 months after the second dose, and 9224.85 U/mL 1 month after a third dose.

Meaning  This study suggests that for patients with cancer undergoing treatment or who received a stem cell transplant, antibody titers peak 1 month after the second dose of a messenger RNA vaccine and are sustained over 6 months; compared with the primary vaccine course, a 20-fold increase in geometric mean titers after a third suggests a robust B-cell response.

Abstract

Importance  The durability of the antibody response to COVID-19 vaccines in patients with cancer undergoing treatment or who received a stem cell transplant is unknown and may be associated with infection outcomes.

Objective  To evaluate anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) and neutralizing antibody (nAb) responses to COVID-19 vaccines longitudinally over 6 months in patients with cancer undergoing treatment or who received a stem cell transplant (SCT).

Design, Setting, and Participants  In this prospective, observational, longitudinal cross-sectional study of 453 patients with cancer undergoing treatment or who received an SCT at the University of Kansas Cancer Center in Kansas City, blood samples were obtained before 433 patients received a messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), after the first dose of the mRNA vaccine, and 1 month, 3 months, and 6 months after the second dose. Blood samples were also obtained 2, 4, and 7 months after 17 patients received the JNJ-78436735 vaccine. For patients receiving a third dose of an mRNA vaccine, blood samples were obtained 30 days after the third dose.

Interventions  Blood samples and BNT162b2, mRNA-1273, or JNJ-78436735 vaccines.

Main Outcomes and Measures  Geometric mean titers (GMTs) of the anti-RBD; the ratio of GMTs for analysis of demographic, disease, and treatment variables; the percentage of neutralization of anti-RBD antibodies; and the correlation between anti-RBD and nAb responses to the COVID-19 vaccines.

Results  This study enrolled 453 patients (mean [SD] age, 60.4 [13,1] years; 253 [56%] were female). Of 450 patients, 273 (61%) received the BNT162b2 vaccine (Pfizer), 160 (36%) received the mRNA-1273 vaccine (Moderna), and 17 (4%) received the JNJ-7846735 vaccine (Johnson & Johnson). The GMTs of the anti-RBD for all patients were 1.70 (95% CI, 1.04-2.85) before vaccination, 18.65 (95% CI, 10.19-34.11) after the first dose, 470.38 (95% CI, 322.07-686.99) at 1 month after the second dose, 425.80 (95% CI, 322.24-562.64) at 3 months after the second dose, 447.23 (95% CI, 258.53-773.66) at 6 months after the second dose, and 9224.85 (95% CI, 2423.92-35107.55) after the third dose. The rate of threshold neutralization (≥30%) was observed in 203 of 252 patients (80%) 1 month after the second dose and in 135 of 166 patients (81%) 3 months after the second dose. Anti-RBD and nAb were highly correlated (Spearman correlation coefficient, 0.93 [0.92-0.94]; P < .001). Three months after the second dose, anti-RBD titers were lower in male vs female patients (ratio of GMTs, 0.52 [95% CI, 0.34-0.81]), patients older than 65 years vs patients 50 years or younger (ratio of GMTs, 0.38 [95% CI, 0.25-0.57]), and patients with hematologic malignant tumors vs solid tumors (ratio of GMTs, 0.40 [95% CI, 0.20-0.81]).

Conclusions and Relevance  In this cross-sectional study, after 2 doses of an mRNA vaccine, anti-RBD titers peaked at 1 month and remained stable over the next 6 months. Patients older than 65 years of age, male patients, and patients with a hematologic malignant tumor had low antibody titers. Compared with the primary vaccine course, a 20-fold increase in titers from a third dose suggests a brisk B-cell anamnestic response in patients with cancer.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: February 7, 2022.

Published Online: April 21, 2022. doi:10.1001/jamaoncol.2022.0752

Correction: This article was corrected on July 21, 2022, to fix errors in the byline and affiliations.

Corresponding Author: Qamar J. Khan, MD, Department of Internal Medicine, The University of Kansas Medical Center, Kansas City, KS 66210 (qkhan@kumc.edu).

Author Contributions: Dr Khan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Sharma and Godwin contributed equally as senior authors.

Concept and design: Khan, Bivona, Zhang, Nelson, Williamson, Sun, Streeter, Mcguirk, Hoffmann, Sharma, Godwin.

Acquisition, analysis, or interpretation of data: Khan, Martin, Zhang, Liu, He, Li, Nelson, Williamson, Doolittle, Sun, Mudaranthakam, Mcguirk, Al-Rajabi, Kasi, Parikh, Zhong, Mitchell, Pessetto, Pathak, Ghosh, LaFaver, Sharma.

Drafting of the manuscript: Khan, Bivona, Mudaranthakam, Mcguirk, Al-Rajabi, Sharma, Godwin.

Critical revision of the manuscript for important intellectual content: Khan, Bivona, Martin, Zhang, Liu, He, Li, Nelson, Williamson, Doolittle, Sun, Mudaranthakam, Streeter, Mcguirk, Hoffmann, Kasi, Parikh, Zhong, Mitchell, Pessetto, Pathak, Ghosh, LaFaver, Sharma, Godwin.

Statistical analysis: Zhang, Liu, He, Nelson, Mudaranthakam, Zhong.

Obtained funding: Khan, Doolittle, Sun, Streeter, Mcguirk, Sharma, Godwin.

Administrative, technical, or material support: Khan, Bivona, Martin, Zhang, Li, Nelson, Sun, Mudaranthakam, Streeter, Mcguirk, Kasi, Parikh, Zhong, Mitchell, Pessetto, Ghosh, LaFaver, Sharma, Godwin.

Supervision: Khan, Bivona, Mudaranthakam, Streeter, Mcguirk, Pessetto, LaFaver, Sharma, Godwin.

Conflict of Interest Disclosures: Dr Zhang reported personal fees from AstraZeneca as a speaker or consultant, grants from AstraZeneca as a principal investigator (PI), personal fees from Bayer as a consultant, grants from Biodesix as a PI, personal fees from Biodesix as a consultant, personal fees from Bristol Myers Squibb as a consultant, personal fees from Cardinal Health as a consultant, personal fees from Daiichi Sankyo as a consultant, personal fees from Hengrui as a consultant, grants from Hengrui as a PI, personal fees from Eli Lilly as a consultant, grants from Mirati as a PI, personal fees from Mirati as a consultant, personal fees from Nexus Health as a consultant, grants from Novartis as a PI, personal fees from Novartis as a consultant, personal fees from Novocure as a consultant, personal fees from Regeneron as a speaker or consultant, personal fees from Sanofi as a speaker or consultant, grants from Genentech as a PI, grants from AbbVie as a PI, grants from BeiGene as a PI, and grants from Nilogen as a PI outside the submitted work. Dr Mcguirk reported personal fees from Kite Pharma, personal fees from Bristol Myers Squibb, personal fees from BioMed, personal fees from GCO, personal fees from G-Med, and personal fees from Mid-America Cancer outside the submitted work. Dr Al-Rajabi reported grants from Bayer for institutional support, grants from NuCana for institutional support, grants from Incyte for institutional support, grants from AstraZeneca for institutional support, grants from Eureka Therapeutics for institutional support, grants from Merck for institutional support, grants from Pfizer for institutional support, holding stockk in Seattle Genetics and Actinium Pharmaceuticals Inc outside the submitted work. Dr Hoffmann reported personal fees from Janssen, personal fees from Pharmacyclics, personal fees from AstraZeneca, personal fees from TG Therapeutics, personal fees from Novartis, and personal fees from BeiGene outside the submitted work. Dr Godwin reported personal fees from Sinochips Diagnostics as the cofounder during the conduct of the study. No other disclosures were reported.

Funding/Support: This work was supported in part by The University of Kansas Cancer Center and the Investigator Initiated Steering Committee, a grant from the National Institute of General Medical Sciences (P20 GM130423), and The University of Kansas Cancer Center Support Grant from the National Cancer Institute (P30 CA168524). Dr Godwin is the Chancellors Distinguished Chair in Biomedical Sciences Endowed.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We acknowledge staff members of The University of Kansas Cancer Center’s Biospecimen Repository Core Facility, including Michele Park and Lauren Dimartino, who are supported, in part, by the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA168524, and the staff members of Sinochips Diagnostics.

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