Chemotherapy modestly reduced immune responses, but not as much as patients and clinicians initially feared.

Vivek Naranbhai, MBChB, PhD, D.Phil
Clinical fellow, Massachusetts General Hospital

BOSTON — Individuals being treated for active cancer have a particularly high risk of severe disease and death from SARS-CoV-2 infection due to their aberrant immune responses from the cancer itself and from some therapies. A new study published in the Journal of Clinical Oncology examines the safety and immunogenicity of SARS-CoV-2 vaccines in a large group of people with diverse cancer types receiving different treatments and is the most comprehensive study of its kind. It is also among the first studies to examine the effect of vaccine booster doses in people with cancer.

“We pursued this study because there were limited data on the safety of SARS-CoV-2 vaccines in people with active cancer; no published prospective clinical trials included this patient population,” says co-lead investigator Justin Gainor, MD, director of the Center for Thoracic Cancers at Massachusetts General Hospital (MGH) and associate professor of Medicine at Harvard Medical School. “There was also considerable uncertainty about how active treatment for cancer would affect the efficacy of the vaccines. Our data are reassuring on both safety and efficacy.”

Adds co-lead investigator Vivek Naranbhai, MBChB, PhD, D.Phil, a clinical fellow at MGH and the Dana-Farber Cancer Institute: “Chemotherapy modestly reduced immune responses, but not as much as patients and clinicians initially feared.”

The study enrolled 1,001 patients with diverse solid-organ and hematologic malignancies treated at the Mass General Cancer Center who had received two doses of the Moderna or Pfizer vaccines or one dose of the Johnson and Johnson vaccine. Thirty-two participants had also received vaccine booster doses.

The investigators measured participants’ concentration of antibodies against SARS-CoV-2 and neutralization titers, which indicates how well the antibodies block the virus from entering cells. Antibody titers and neutralization titers are proxy measures that correlate with protection against COVID-19 infection.

The investigators found that the type of vaccine participants received was a major factor in inducing immune responses. Patients who received the J&J vaccine had considerably lower immune responses than participants who received mRNA vaccines—Pfizer and Moderna—which is consistent with what has been previously observed in healthy controls. Collectively, however, cancer patients’ responses to the three vaccines are modestly impaired relative to healthy people, but most patients have responses that are likely to be sufficient to protect against severe disease. “Our data suggest that patients with cancer should receive mRNA vaccines,” says Gainor. “In addition, patients who received the J&J vaccine should be considered for additional vaccine doses.”

Additional doses of the vaccine in the small group of participants who received them were safe and well-tolerated and induced higher immune responses. The CDC now recommends that people who are immunocompromised, including people with cancer, and older patients receive additional doses of vaccine.

Participants who had prior COVID-19 infection also had higher immune responses to the vaccine, whereas increasing age predicted lower responses, and immunity induced by all the vaccines declined over time.

Cancer treatment had a smaller effect on immune responses than the type of vaccine participants received. Patients who received chemotherapy, bone marrow transplants, or corticosteroids had lower immune responses, but most were predicted to still be protective. Individuals who received treatments with immune checkpoint blockade tended to have enhanced immune responses.

“The vaccine side effects experienced by patients with cancer were similar to those experienced by healthy controls and were generally mild or moderate, which should be reassuring to patients,” says Naranbhai. Individuals who reported worse side effects had slightly better immune responses, and patients with prior COVID-19 infection also had more significant reactions to the vaccine.

Next steps for this research include a deeper exploration of how different approaches to cancer treatment affect immune responses and how the vaccines may generate responses against potential new SARS-CoV-2 variants in patients with cancer. “We are also trying to learn more about how vaccines in general perform in patients with cancer, which may help advance ongoing research in vaccines for the treatment of cancer,” says Naranbhai.

The Lambertus Foundation and Donald Glazer provided funding for this study.

Other key authors of this study include co-lead investigator A. John Iafrate, MD, PhD, vice chair of Pathology at MGH and professor of Pathology at HMS; Ryan Sullivan, MD, associate director of the Melanoma program at MGH and associate professor of Medicine at HMS; Aditya Bardia, MD, MPH, director of Precision Medicine, Center for Breast Cancer at MGH and assistant professor in Medicine at HMS; and Alejandro Balazs, PhD, a Core Member at the Ragon Institute of MGH, MIT and Harvard.

About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of “America’s Best Hospitals.”