[Skip to Content]
[Skip to Content Landing]

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

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.

References
1.
Bakouny  Z , Hawley  JE , Choueiri  TK ,  et al.  COVID-19 and cancer: current challenges and perspectives.   Cancer Cell. 2020;38(5):629-646. PubMedGoogle ScholarCrossref
2.
Al-Shamsi  HO , Alhazzani  W , Alhuraiji  A ,  et al.  A practical approach to the management of cancer patients during the novel coronavirus disease 2019 (COVID-19) pandemic: an international collaborative group.   Oncologist. 2020;25(6):e936-e945. PubMedGoogle ScholarCrossref
3.
Sharma  A , Bhatt  NS , St Martin  A ,  et al.  Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study.   Lancet Haematol. 2021;8(3):e185-e193. PubMedGoogle ScholarCrossref
4.
Boyarsky  BJ , Werbel  WA , Avery  RK ,  et al.  Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients.   JAMA. 2021;325(17):1784-1786. PubMedGoogle ScholarCrossref
5.
Hall  VG , Ferreira  VH , Ku  T ,  et al.  Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients.   N Engl J Med. 2021;385(13):1244-1246. PubMedGoogle ScholarCrossref
6.
Mueller  T .  Antibodies against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in individuals with and without COVID-19 vaccination: a method comparison of two different commercially available serological assays from the same manufacturer.   Clin Chim Acta. 2021;518:9-16. PubMedGoogle ScholarCrossref
7.
Terpos  E , Trougakos  IP , Apostolakou  F ,  et al.  Age-dependent and gender-dependent antibody responses against SARS-CoV-2 in health workers and octogenarians after vaccination with the BNT162b2 mRNA vaccine.   Am J Hematol. 2021;96(7):E257-E259. PubMedGoogle ScholarCrossref
8.
Turner  JS , O’Halloran  JA , Kalaidina  E ,  et al.  SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.   Nature. 2021;596(7870):109-113. PubMedGoogle ScholarCrossref
9.
Schmidt  AL , Labaki  C , Hsu  CY ,  et al; COVID-19 and Cancer Consortium.  COVID-19 vaccination and breakthrough infections in patients with cancer.   Ann Oncol. 2022;33(3):340-346. PubMedGoogle ScholarCrossref
10.
Bergwerk  M , Gonen  T , Lustig  Y ,  et al.  Covid-19 breakthrough infections in vaccinated health care workers.   N Engl J Med. 2021;385(16):1474-1484. PubMedGoogle ScholarCrossref
11.
Gilbert  PB , Montefiori  DC , McDermott  A ,  et al.  Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy trial.   medRxiv. Preprint posted online January 1, 2021. Google Scholar
12.
Khoury  DS , Cromer  D , Reynaldi  A ,  et al.  Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.   Nat Med. 2021;27(7):1205-1211. PubMedGoogle ScholarCrossref
13.
McMahan  K , Yu  J , Mercado  NB ,  et al.  Correlates of protection against SARS-CoV-2 in rhesus macaques.   Nature. 2021;590(7847):630-634. PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close