Humoral Responses After SARS-CoV-2 mRNA Vaccination and Breakthrough Infection in Cancer Patients

Abstract

Objective: To evaluate the magnitude of humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients with cancer receiving active therapies.

Patients and methods: Patients 18 years or older in whom SARS-CoV-2 spike antibody (anti-S Ab) levels were measured after 2 doses of SARS-CoV-2 mRNA vaccines were included. Patients with prior coronavirus disease 2019 (COVID-19) infection or receiving 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 while receiving treatments associated with cytopenia, including chemotherapy or cyclin-dependent kinase 4 and 6 inhibitors. A significantly greater proportion of immunocompetent patients (96.7% [59 of 61]) had anti-S Ab titers of 500 U/mL or greater compared to patients with hematologic (7.7% [7 of 91) and solid (55.1% [27 of 49]) malignancy (P<.001). Despite 2 doses of SARS-CoV-2 mRNA vaccines, 52.7% of patients with hematologic malignancy (48 of 91) and 8.2% of those with solid malignancy (4 of 49) receiving cytopenic therapy had no seroconversion (spike antibody titers <0.8 U/mL). Two patients subsequently had development of breakthrough COVID-19 infection after full vaccination.

Conclusion: A substantial proportion of patients with hematologic and solid malignancies receiving chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. Our study adds to a growing body of literature suggesting that immunosuppressed patients have a suboptimal humoral response to COVID-19 vaccination. Our study also underscores the importance of assessing antibody response after COVID-19 vaccines in these vulnerable patients.

Keywords: Anti-S Ab, SARS-CoV-2 spike antibody; CDK4/6i, cyclin-dependent kinase 4 and 6 inhibitor(s); CLL, chronic lymphocytic leukemia; COVID-19, coronavirus disease 2019; OR, odds ratio; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; mRNA, messenger RNA.

Figure

Box plot of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibody titer in healthy individuals and patients with cancer not receiving immunosuppressive therapy (immunocompetent group), hematologic malignancy group, and those receiving systemic therapies associated with cytopenia (solid malignancy on cytopenic treatment group). Patients with titers of 2500 U/mL or higher were assigned the value of 2500 U/mL and those with titers of less than 0.8 U/mL were assigned the value of 0 U/mL.