[Skip to Content]
[Skip to Content Landing]
Key Points

Question  Does the immune response to the mRNA-1273 vaccine differ among patients with solid tumors and hematologic cancer?

Findings  In this cohort study of 515 patients with cancer, seropositivity after the first and second vaccine doses was 71% and 90%, respectively. Antibody levels after vaccination were substantially higher among patients who were seropositive before vaccination.

Meaning  Results of this study suggest that the mRNA-1273 vaccine induced a highly variable seroconversion percentage among patients with cancer; these patients may benefit from additional vaccine doses.

Abstract

Importance  Patients with cancer experience high rates of morbidity and mortality after SARS-CoV-2 infection. Immune response to mRNA-1273 vaccination across multiple cancer types and treatments remains to be established.

Objective  To quantitate antibody responses after mRNA-1273 vaccination among patients with solid tumors and hematologic cancer and to assess clinical and treatment factors associated with vaccine response.

Design, Setting, and Participants  This cohort study included patients with cancer who were aged 18 years or older, spoke English or Spanish, had received their first mRNA-1273 dose between January 12 and 25, 2021, and agreed to blood tests before and after vaccination.

Exposures  Receipt of 1 and 2 mRNA-1273 SARS-CoV-2 vaccine doses.

Main Outcomes and Measures  Seroconversion after each vaccine dose and IgG levels against SARS-CoV-2 spike protein obtained immediately before the first and second vaccine doses and 57 days (plus or minus 14 days) after the first vaccine dose. Cancer diagnoses and treatments were ascertained by medical record review. Serostatus was assessed via enzyme-linked immunosorbent assay. Paired t tests were applied to examine days 1, 29, and 57 SARS-CoV-2 antibody levels. Binding antibody IgG geometric mean titers were calculated based on log10-transformed values.

Results  The 515 participants were a mean (SD) age of 64.5 (11.4) years; 262 (50.9%) were women; and 32 (6.2%) were Hispanic individuals and 479 (93.0%) White individuals; race and ethnicity data on 4 (0.7%) participants were missing. Seropositivity after vaccine dose 2 was 90.3% (465; 95% CI, 87.4%-92.7%) among patients with cancer, was significantly lower among patients with hematologic cancer (84.7% [255]; 95% CI, 80.1%-88.6%) vs solid tumors (98.1% [210]; 95% CI, 95.3%-99.5%), and was lowest among patients with lymphoid cancer (70.0% [77]; 95% CI, 60.5%-78.4%). Patients receiving a vaccination within 6 months after anti-CD20 monoclonal antibody treatment had a significantly lower seroconversion (6.3% [1]; 95% CI, 0.2%-30.2%) compared with those treated 6 to 24 months earlier (53.3% [8]; 95% CI, 26.6%-78.7%) or those who never received anti-CD20 treatment (94.2% [456]; 95% CI, 91.7%-96.1%). Low antibody levels after vaccination were observed among patients treated with anti-CD20 within 6 months before vaccination (GM, 15.5 AU/mL; 95% CI, 9.8-24.5 AU/mL), patients treated with small molecules (GM, 646.7 AU/mL; 95% CI, 441.9-946.5 AU/mL), and patients with low lymphocyte (GM, 547.4 AU/mL; 95% CI, 375.5-797.7 AU/mL) and IgG (GM, 494.7 AU/mL; 95% CI, 304.9-802.7 AU/mL) levels.

Conclusions and Relevance  This cohort study found that the mRNA-1273 SARS-CoV-2 vaccine induced variable antibody responses that differed by cancer diagnosis and treatment received. These findings suggest that patients with hematologic cancer and those who are receiving immunosuppressive treatments may need additional vaccination doses.

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: December 21, 2021.

Published Online: March 10, 2022. doi:10.1001/jamaoncol.2022.0001

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Giuliano AR et al. JAMA Oncology.

Corresponding Author: Anna R. Giuliano, PhD, Moffitt Cancer Center, MRC-CANCONT, 12902 Magnolia Dr, Tampa, FL 33612 (anna.giuliano@moffitt.org).

Author Contributions: Dr Giuliano had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Giuliano, Lancet, Pilon-Thomas, Dong, Tan, Tworoger, Siegel, Mo, Cubitt, Dukes.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Giuliano, Lancet, Pilon-Thomas, Tan, Ball, Cubitt, Dukes, Hensel.

Critical revision of the manuscript for important intellectual content: Giuliano, Lancet, Pilon-Thomas, Dong, Jain, Tworoger, Siegel, Whiting, Mo, Cubitt, Dukes, Hensel, Keenan, Hwu.

Statistical analysis: Dong, Whiting, Mo.

Obtained funding: Giuliano, Tworoger.

Administrative, technical, or material support: Pilon-Thomas, Dong, Jain, Tan, Tworoger, Cubitt, Dukes, Hensel, Keenan, Hwu.

Supervision: Giuliano, Pilon-Thomas, Ball, Cubitt.

Conflict of Interest Disclosures: Dr Giuliano reported receiving grants from Merck & Co, Inc, through Moffitt Cancer Center and personal fees from Merck & Co, Inc, as an advisory board member outside the submitted work. Dr Lancet reported receiving personal fees from Novartis, Bristol Myers Squibb, AbbVie, Astellas Pharma, Takeda Pharmaceutical Co, Daiichi Sankyo, Jazz Pharmaceuticals, Agios Pharmaceuticals, ElevateBio, and Jasper Therapeutics, Inc, outside the submitted work. Dr Tworoger reported receiving grants from the US Department of Defense, Florida Department of Health, and the National Institutes of Health outside the submitted work. Dr Hwu reported receiving grants from Merck & Co, Inc, and from the National Cancer Institute–designated comprehensive cancer center funded in part by a Moffitt Cancer Center support grant during the conduct of the study; he reported receiving personal fees from the Dragonfly Scientific Advisory Board and Immatics Scientific Advisory Board outside the submitted work. No other disclosures were reported.

Funding/Support: This work was funded in part by the Moffitt Cancer Center’s support grant P30CA076292, which supported the center’s Total Cancer Care staff; Chemical Biology Core; the Participant Research, Interventions, and Measurement Core; Cancer Pharmacokinetics and Pharmacodynamics Core; Tissue Core; and Biostatistics and Bioinformatics Shared Resource Core. The state of Florida funds provided to the Moffitt Center for Immunization and Infection Research in Cancer also supported this study. This work was additionally supported in part by research grant MISP 60276 from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance contract HHSN272201400008C.

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 thank the staff of the Krammer Laboratory at the Icahn School of Medicine at Mount Sinai for providing receptor binding domain and spike expression vectors. We also thank Ligia Pinto, PhD, Frederick National Laboratory for Cancer Research, for the methods to measure IgG responses against the receptor binding domain and S proteins of SARS-CoV-2. They did not receive compensation beyond their usual salary for their contribution to this study.

References
1.
Grivas  P , Khaki  AR , Wise-Draper  TM ,  et al.  Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.   Ann Oncol. 2021;32(6):787-800. doi:10.1016/j.annonc.2021.02.024 PubMedGoogle ScholarCrossref
2.
Thakkar  A , Gonzalez-Lugo  JD , Goradia  N ,  et al.  Seroconversion rates following COVID-19 vaccination among patients with cancer.   Cancer Cell. 2021;39(8):1081-1090.e2. doi:10.1016/j.ccell.2021.06.002 PubMedGoogle ScholarCrossref
3.
Massarweh  A , Eliakim-Raz  N , Stemmer  A ,  et al.  Evaluation of seropositivity following BNT162b2 messenger RNA vaccination for SARS-CoV-2 in patients undergoing treatment for cancer.   JAMA Oncol. 2021;7(8):1133-1140. doi:10.1001/jamaoncol.2021.2155 PubMedGoogle ScholarCrossref
4.
Amanat  F , Stadlbauer  D , Strohmeier  S ,  et al.  A serological assay to detect SARS-CoV-2 seroconversion in humans.   Nat Med. 2020;26(7):1033-1036. doi:10.1038/s41591-020-0913-5PubMedGoogle ScholarCrossref
5.
Stadlbauer  D , Amanat  F , Chromikova  V ,  et al.  SARS-CoV-2 seroconversion in humans: a detailed protocol for a serological assay, antigen production, and test setup.   Curr Protoc Microbiol. 2020;57(1):e100. doi:10.1002/cpmc.100 PubMedGoogle ScholarCrossref
6.
Giuliano  AR , Pilon-Thomas  S , Schell  MJ ,  et al.  SARS-CoV-2 period seroprevalence and related factors: Hillsborough County, Florida, October 2020-March 2021.   Emerg Infect Dis. 2022;28(3). Published online January 26, 2022. doi:10.3201/eid2803.211495PubMedGoogle ScholarCrossref
7.
Greenberger  LM , Saltzman  LA , Senefeld  JW , Johnson  PW , DeGennaro  LJ , Nichols  GL .  Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies.   Cancer Cell. 2021;39(8):1031-1033. doi:10.1016/j.ccell.2021.07.012 PubMedGoogle ScholarCrossref
8.
COVID-19 vaccines for moderately to severely immunocompromised people. Centers for Disease Control and Prevention. Updated January 7, 2022. Accessed August 17, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html
9.
Agha  ME , Blake  M , Chilleo  C , Wells  A , Haidar  G .  Suboptimal response to coronavirus disease 2019 messenger RNA vaccines in patients with hematologic malignancies: a need for vigilance in the postmasking era.   Open Forum Infect Dis. 2021;8(7):ofab353. doi:10.1093/ofid/ofab353 PubMedGoogle ScholarCrossref
10.
Pleyer  C , Ali  MA , Cohen  JI ,  et al.  Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines.   Blood. 2021;137(2):185-189. doi:10.1182/blood.2020008758 PubMedGoogle ScholarCrossref
11.
Doria-Rose  N , Suthar  MS , Makowski  M ,  et al; mRNA-1273 Study Group.  Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19.   N Engl J Med. 2021;384(23):2259-2261. doi:10.1056/NEJMc2103916 PubMedGoogle ScholarCrossref
12.
Wu  K , Werner  AP , Koch  M ,  et al.  Serum neutralizing activity elicited by mRNA-1273 vaccine.   N Engl J Med. 2021;384(15):1468-1470. doi:10.1056/NEJMc2102179 PubMedGoogle ScholarCrossref
13.
Abu-Raddad  LJ , Chemaitelly  H , Butt  AA ; National Study Group for COVID-19 Vaccination.  Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants.   N Engl J Med. 2021;385(2):187-189. doi:10.1056/NEJMc2104974 PubMedGoogle ScholarCrossref
14.
Jalkanen  P , Kolehmainen  P , Häkkinen  HK ,  et al.  COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants.   Nat Commun. 2021;12(1):3991. doi:10.1038/s41467-021-24285-4 PubMedGoogle ScholarCrossref
15.
Anderson  EJ , Rouphael  NG , Widge  AT ,  et al; mRNA-1273 Study Group.  Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults.   N Engl J Med. 2020;383(25):2427-2438. doi:10.1056/NEJMoa2028436 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