key: cord-0886724-rg52w4vx
authors: Chumsri, Saranya; Advani, Pooja P.; Pai, Tanmayi S.; Li, Zhuo; Mummareddy, Ashita; Acampora, Marites; Reynolds, Gina A.; Wylie, Natasha; Boyle, Ashton W.; Lou, Yanyan; Mody, Kabir; Moreno-Aspitia, Alvaro; Swift, Melanie D.; Virk, Abinash; Bharucha, Adil E.; Marquez, Christopher P.; Patel, Tushar C.; Gores, Gregory J.; Knutson, Keith L.
title: Humoral Responses after SARS-CoV-2 mRNA Vaccination and Breakthrough Infection in Cancer Patients
date: 2021-12-13
journal: Mayo Clin Proc Innov Qual Outcomes
DOI: 10.1016/j.mayocpiqo.2021.12.004
sha: 989223d73883abaaacb5677e3710b267fa1c31cc
doc_id: 886724
cord_uid: rg52w4vx

Objective To evaluate the magnitude of humoral response to SARS-CoV-2 mRNA vaccines in cancer patients on active therapies. Patients and Methods Patients ≥ 18 years in whom SARS-CoV-2 spike antibody (anti-S Ab) were measured after 2 doses of SARS-CoV-2 mRNA vaccines were included. Patients with prior COVID-19 infection or on other immunosuppressive therapy were excluded. Results Among 201 patients who met the criteria, 61 were immunocompetent, 91 had a hematologic malignancy, and 49 had a solid malignancy on treatments associated with cytopenia, including chemotherapy or cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). Significantly greater proportion of immunocompetent patients (97%) had anti-S Ab titer ≥ 500 U/mL compared to patients with hematologic (8%) and solid malignancy (55%, p < 0.001). Despite 2 doses of SARS-CoV-2 mRNA vaccines, 53% of hematologic malignancy patients and 8% of solid malignancy patients on cytopenic therapy had no seroconversion (< 0.8 U/mL). Two patients subsequently developed breakthrough COVID-19 infection after full vaccination. Conclusions A substantial proportion of patients with hematologic and solid malignancies on chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. Our study adds to growing body of literature suggesting that immunosuppressed patients have suboptimal humoral response to COVID-19 vaccination. Our study also underscores the significance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.

SARS-CoV-2 mRNA vaccines have been demonstrated to have remarkable efficacy in healthy individuals with robust and durable humoral immune response [1] [2] [3] [4] . While SARS-CoV-2 mRNA vaccines are highly effective in healthy individuals, their effectiveness in immunocompromised patients remains less known. Emerging data suggests that cancer patients may not mount adequate protective immune response after SARS-CoV-2 infection 5 

BNT162b2 (Pfizer/BioNTech) [6] [7] [8] . Limited data is available with mRNA-1273 (Moderna/National Institutes of Health).

We conducted a retrospective cross-sectional study of patients ≥ 18 years old who had anti-S Ab performed after 2 doses of SARS-CoV-2 mRNA vaccines between 12-90 days at the 3 Mayo Clinic sites in Minnesota, Florida, and Arizona between January 1, 2021 and May 10, 2021. The Elecsys Anti-SARS-CoV-2 S electrochemiluminescence immunoassay (Roche Diagnostics, Switzerland) was used to measure the antibody response. Patients with prior COVID-19 infection and patients on immunosuppressive therapy for an indication other than cancer were excluded. This study was approved by the Mayo Clinic Institutional Review Board.

Categorical variables were summarized as frequencies (percentages) and continuous variables were reported as median with range. Wilcoxon signed rank test was used to compare continuous variables between groups and Chi-squared or Fisher's exact test was used to compare categorical variables. For boxplot depiction, patients with anti-S Ab level of > 2,500 U/mL were assigned J o u r n a l P r e -p r o o f the value of 2,500 U/mL and < 0.4 U/mL were assigned the value of 0 U/mL. All tests were twosided with p value < 0.05 considered statistically significant. The analysis was done using R program version 3.6.2.

Among 611 patients in whom anti-S Ab were assessed, 201 patients met the inclusion criteria and were included in this analysis ( The median age in hematology malignancy group was older at 71 years compared to 68 years in immunocompetent group and 66 years in solid malignancy group (p < 0.001). More patients with a hematology malignancy group were men (63 patients, 69.2%) vs 8 patients (13.8%) in the immunocompetent group and 2 patients (4.1%) with a solid malignancy (p < 0.001).

Ninety-five (47.3%) patients received mRNA-1273 and 106 (52.7%) patients received BNT162b2 (Table 2) In solid malignancy group, 4 (8.2%) patients had negative result, and 10 (20.4%) patients had values ≤ 50 U/mL. Among patients who received CDK4/6i, 4 (28.6%) patients had anti-S Ab ≤ 500 U/mL compared to. 20 (54.1%) patients in patients who receive chemotherapy. However, this difference did not reach statistically significant level (p = 0.1, Supplemental Figure 1 ). The best of our knowledge, our study was the first study to evaluate immune response in cancer patients receiving either BNT162b2 or mRNA-1273 using the same anti-S Ab assay. Although receiving BNT162b2 was associated with lower anti-S Ab after adjusting for age, gender, and treatment groups, there were significantly more number of hematologic malignancy patients J o u r n a l P r e -p r o o f receiving BNT162b2. Therefore, this result should be interpreted with caution. Furthermore, our study also illustrated patients who developed break through infection after full vaccination.

While CDK4/6i is not generally considered as immunosuppressive therapy, our study demonstrated that these patients may also have an impaired antibody-mediated response to SARS-CoV-2 mRNA vaccines. When comparing to chemotherapy, there were numerically less percentage of patients receiving CDK4/6i with anti-S Ab ≤ 500 U/mL (28.6%) compared to chemotherapy (54.1%). Although this difference did not reach statistically significant level, it is likely due to small sample size.

Our study has limitations, particularly being a retrospective study and there were imbalances in age, gender and type of vaccine as described. While there were imbalances in gender and age between each of the groups, gender and age itself were not significantly associated with lower anti-S Ab levels. In addition, our current study only focused on the levels of anti-S Ab. The neutralizing capacity of these antibodies and the cellular T-cell responses to these vaccines remain unknown. Additional studies are needed to further define the optimal antibody response that provides J o u r n a l P r e -p r o o f Difference between health/immunocompetent vs. hematologic malignancy patients, and immunocompetent vs. solid tumor patients were both significant at < 0.001 level.

Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2

Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS

CoV-2 Vaccine

Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan

Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer

Safety and immunogenicity of one versus two