Evaluation of Antibody Response to SARS-CoV-2 mRNA-1273 Vaccination in Patients With Cancer in Florida

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.

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.

Patients with cancer have many risk factors for poor SARS-CoV-2 infection outcomes,¹ underscoring an urgency for vaccination. Some reports have indicated suboptimal responses to vaccination among patients with cancer, although sample sizes were small, limiting comparisons across disease and treatment characteristics.^2,3 The humoral response kinetics to the mRNA-1273 vaccination among patients with cancer has not been fully evaluated.

We conducted an observational study with the primary and secondary aims of quantitating antibody responses before and after SARS-CoV-2 mRNA-1273 vaccination among patients diagnosed with solid tumors and hematologic cancer and to assess clinical and treatment factors associated with antibody levels after vaccination. We also assessed whether antibody status before vaccination was associated with antibody levels achieved after 2 vaccine doses.

All of the patients in this cohort study had cancer and were sequentially enrolled from those presenting for mRNA-1273 vaccination at Moffitt Cancer Center between January 12 and 25, 2021. Patients provided one 10-mL tiger-top blood sample before the first and second vaccine doses (days 1 and 29) and on day 57 (plus or minus 14 days). Patients met study eligibility requirements if they provided written informed consent to Total Cancer Care; were aged 18 years or older; spoke English or Spanish; had received their first mRNA-1273 dose at the Moffitt Cancer Center between January 12 and 25, 2021; and agreed to blood tests before and after vaccination. Patients were excluded if they did not provide consent, declined the blood draws, or indicated they could not attend visits after vaccination. Blood collection occurred under an Advarra Institutional Review Board–approved Total Cancer Care protocol; specimen retrieval and analyses occurred under a separate protocol. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

A total of 863 patients were approached, 690 were enrolled, and 175 were excluded, with a final sample size of 515 patients (eFigure in the Supplement). The patients self-reported race and ethnicity. Retrospective medical record review was used to ascertain cancer diagnoses and treatments.

Serostatus was assessed via enzyme-linked immunosorbent assay adapted from the Krammer protocol.^4,5 Negative controls included serum pools from individuals witout cancer collected before 2015. Positive controls included convalescent serum from patients without cancer who tested positive for COVID-19. Antibody levels were quantitated using the Human SARS-CoV-2 Serology Standard provided by the Frederick National Laboratory for Cancer Research. eTable 1 in the Supplement includes details and quality control results.

For comparison, antibody levels obtained 14 to 60 days after mRNA-1273 vaccination from 18 adults without cancer aged 24 to 72 years, who participated in a separate community study performed by some of us, were quantitated.⁶

Patient characteristics were summarized using descriptive statistics (mean [SD] for continuous variables and proportions and frequencies for categorical measures). SARS-CoV-2 antibody positivity was compared across patient characteristics using the Fisher exact or χ² test. The association of SARS-CoV-2 antibody levels and patient characteristics was examined using the Kruskal-Wallis test. Paired t tests were applied to examine SARS-CoV-2 antibody levels on days 1, 29, and 57. Binding antibody IgG geometric mean titers were calculated based on log₁₀-transformed values. Observations with missing data were removed from the analysis. All analyses were performed using SAS, version 9.4 (SAS Institute, Inc) and R software, version 4.0.2 (R Foundation for Statistical Computing). Raw P values were corrected for multiple comparisons using the Bonferroni method, and adjusted 2-sided P < .05 was considered to be statistically significant.

Of 515 participants with a mean (SD) age of 64.5 (11.4) years, 262 (50.9%) were women, 253 (49.1%) were men, 32 (6.2%) were Hispanic individuals, and 479 (93.0%) were White individuals (race and ethnicity data on 4 [0.7%] participants were missing). There were 301 (58.4%) patients with hematologic cancer and 214 (41.6%) with solid tumors. Seventeen (3.3%) patients were SARS-CoV-2 seropositive before vaccination (Table 1).

Overall, 71.3% (367; 95% CI, 67.1%-75.1%) and 90.3% (465; 95% CI, 87.4%-92.7%) of patients seroconverted after 1 and 2 vaccine doses, respectively (Table 1). Seroconversion after the second vaccine dose was lower among patients with hematologic cancer vs solid tumors (84.7% [255]; 95% CI, 80.1%-88.6% vs 98.1% [210]; 95% CI, 95.3%-99.5%). Within the hematologic cancer category, patients with lymphoid cancer had a low seroconversion percentage (70.0% [77]; 95% CI, 60.5%-78.4%), particularly among patients with chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma (65.2% [15 of 23] and 58.2% [32 of 55], respectively; eTable 2 in the Supplement). The response was lowest among patients with chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma receiving treatment (30.4% [7 of 23]) vs not receiving treatment (72.7% [40 of 55]). Patients treated with anti-CD20 monoclonal antibodies within 6 months before vaccination had a significantly lower seroconversion percentage (6.3% [1]; 95% CI, 0.2%-30.2%) vs patients who received treatment 6 to 24 months before vaccination (53.3% [8]; 95% CI, 26.6%-78.7%) and those not receiving this treatment (94.2% [456]; 95% CI, 91.7%-96.1%). After 2 vaccine doses, a low seroconversion percentage was also observed among patients treated with Bruton tyrosine kinase (BTK) inhibitors (33.3% [2 of 6]; 95% CI, 4.3%-77.7%), PI3K inhibitors (0%), or venetoclax (50.0% [3 of 6]; 95% CI, 11.8%-88.2%), and patients who underwent CD19 chimeric antigen receptor T-cell (CAR-T) therapy (12.5% [1 of 8]; 95% CI, 0.3%-52.7%; eTable 2 in the Supplement). In contrast, 100% of patients with autologous transplant treated within 12 months and those treated with B-cell maturation antigen CAR-T seroconverted after 2 doses (Table 1; and eTable 2 in the Supplement). Seroconversion percentages among patients with allogeneic hematopoietic stem cell transplant were high.

After vaccination, significantly higher antibody levels were observed among adults without cancer who participated in a separate community study⁶ (geometric mean [GM], 7303.7 arbitrary units (AU)/mL; 95% CI, 3906.8-13 654.2 AU/mL) vs patients with solid tumors (GM, 1754.6 AU/mL; 95% CI, 1502.7-2048.8 AU/mL) or hematologic cancer (GM, 745.6 AU/mL; 95% CI, 579.0-960.2 AU/mL), and among patients with cancer who were seropositive on day 1 (GM, 6821.0 AU/mL; 95% CI, 3530.1-13 179.4 AU/mL) vs seronegative (GM, 998.6 AU/mL; 95% CI, 845.4-1179.6 AU/mL) (Figure). Low antibody levels after vaccination were observed among patients with low lymphocyte (GM, 547.4 AU/mL; 95% CI, 375.7-797.7 AU/mL) and low IgG levels (GM, 494.7 AU/mL; 95% CI, 304.9-802.7 AU/mL) and among patients treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (GM, 15.5 AU/mL; 95% CI, 9.8-24.5 AU/mL) or treated with small molecules, including tyrosine kinase inhibitors, proteasome inhibitors, lenalidomide, pomalidomide, and ventoclax (GM, 646.7; 95% CI, 441.9-946.5 AU/mL) (Table 2). eTable 3 in the Supplement shows the large range of achieved antibody levels after vaccination stratified by cancer diagnosis and treatment type, with especially low levels observed among patients with chronic lymphocytic leukemia and those treated with BTK inhibitors and venetoclax.

This large study of patients with cancer enabled direct comparisons across multiple cancer diagnoses and treatments in patients who received 2 mRNA-1273 vaccine doses. Chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma had the lowest seroconversion percentages and antibody levels, consistent with other studies.⁷ Noteworthy was the complete lack of an antibody response in patients treated with anti-CD20 monoclonal antibodies and low seroconversion percentages among those treated with BTK inhibitors, venetoclax, and CD19-CAR-T. After the second dose, antibody levels were higher among patients who were seropositive at baseline compared with those who were seronegative. After 2 vaccine doses, patients who had a seropositive status before vaccination achieved antibody levels similar to those of adults without cancer, suggesting that patients with cancer with initially poor immune responses may benefit from additional vaccine doses, including a third dose, as recently recommended.⁸

Hematologic cancer is characterized by B-cell defects associated with lower rates of antibody response to vaccines, even in the absence of anticancer therapy.^9,10 Seroconversion percentages among patients with allogeneic hematopoietic stem cell transplant were high. Patients receiving CD19-CAR-T had low seroconversion percentages, though most received CAR-T more than 1 year before the study, were in remission, and had not received cancer treatment in the past year, suggesting prolonged immunosuppression after CD19-CAR-T therapy.

Antibody levels required to confer protection against SARS-CoV-2 are unknown. However, lower initial antibody levels are of concern because levels decline over time,¹¹ higher levels are needed to neutralize variants of concern,^12-14 and new variants continue to emerge. Patients who had seropositive status before the start of vaccination had antibody levels similar to levels after 1 vaccine dose and substantially higher levels after 2 doses than patients with initially seronegative status. It remains to be tested whether a third dose will overcome the poor vaccine response among patients who did not seroconvert or had very low antibody levels.¹⁵

This study has limitations. Despite having a large sample size of patients with cancer, we were limited in our sample of patients who received certain targeted therapies (eg, BTK inhibitors, venetoclax, CD19-CAR-T, and B-cell maturation antigen CAR-T).

Findings of this cohort study suggest that patients with solid tumors or hematologic cancer have an immune response after COVID-19 vaccination, although with lower antibody levels than adults without cancer who participated in a separate community study.⁶ Patients with hematologic cancer and those who are receiving immunosuppressive treatments may need to be given priority for the third dose of vaccination, with careful consideration given to the timing of vaccination relative to the receipt of cancer treatment.⁸

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.