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.”
Journal of Clinical Oncology
Method of Research
Subject of Research
Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study
Article Publication Date
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Laura M. Spring Consulting or Advisory Role: Novartis, Avrobio Research Funding: Tesaro (Inst), Merck (Inst) Travel, Accommodations, Expenses: Merck, Tesaro Steven J. Isakoff Consulting or Advisory Role: AbbVie, OncoPep, Puma Biotechnology, Seattle Genetics, Novartis, Paxman Coolers Ltd Research Funding: Genentech (Inst), PharmaMar (Inst), AbbVie (Inst), OncoPep (Inst), Merck (Inst), AstraZeneca/MedImmune (Inst), Outcomes4Me (Inst) Jocelyn R. Farmer Consulting or Advisory Role: Bristol Myers Squibb Foundation Research Funding: Bristol Myers Squibb Foundation Leyre Zubiri Consulting or Advisory Role: Merck Gabriela S. Hobbs Consulting or Advisory Role: Incyte, AbbVie, Novatis, Blueprint Medicines, Keros Therapeutics Research Funding: Incyte, Constellation Pharmaceuticals Andrew M. Brunner Consulting or Advisory Role: Celgene, Novartis, Takeda, Agios, Bristol Myers Squibb/Celgene, Acceleron Pharma Research Funding: Celgene, Takeda, Novartis, GlaxoSmithKline, AstraZeneca Amir T. Fathi Consulting or Advisory Role: Agios, Novartis, Takeda, Astellas Pharma, Daiichi Sankyo, Bristol Myers Squibb, Forty Seven, AbbVie, Kite, a Gilead Company, Trovagene, Pfizer, Seattle Genetics, Amgen, Trillium Therapeutics, Blueprint Medicines, Kura Oncology, Foghorn Therapeutics, Genentech, Ipsen, MorphoSys, Servier Research Funding: Takeda (Inst), Agios (Inst), Bristol Myers Squibb (Inst), AbbVie (Inst), Servier (Inst) Brittany Y. Bertaux Employment: Partners (I) Elizabeth Niehoff Stock and Other Ownership Interests: Biogen Inc, Blueprint Medicines, Crispr Therapeutics, InVitae, LabCorp, Natera Inc, Pacific Biosciences Christian N. Nambu Employment: Massachusetts General Hospital Cancer Center, AFC Urgent Care (I) Stock and Other Ownership Interests: Moderna Therapeutics Onosereme Ofoman Employment: Massachusetts General Hospital Kerry Reynolds Employment: Teladoc Stock and Other Ownership Interests: Biogen (I) Other Relationship: Project DataSphere Henning Willers Research Funding: Apple Inc Wilfredo-Garcia Beltran Patents, Royalties, Other Intellectual Property: European Patent—New therapy for treating graft-versus-host disease (EP3575320A1) Kimberly Blumenthal Leadership: Novocardia (I) Stock and Other Ownership Interests: Devoted Health (I), Novocardia (I) Honoraria: UpToDate, GA²LEN ANACARE Research Funding: National Institute of Health (NIH)—K01AI125631, Massachusetts General Hospital, Transformative Scholar Award Ryan J. Sullivan Consulting or Advisory Role: Novartis, Merck, Replimune, Asana Biosciences, Alkermes, Eisai, Pfizer, Iovance Biotherapeutics, OncoSec, AstraZeneca, Bristol Myers Squibb Research Funding: Amgen (Inst), Lilly (Inst), BioMed Valley Discoveries (Inst), Merck (Inst), Deciphera (Inst), Roche/Genentech (Inst), Moderna Therapeutics (Inst), Sanofi (Inst), Aeglea Biotherapeutics (Inst), Asana Biosciences (Inst), Viralytics (Inst), Compugen (Inst), Neon Therapeutics (Inst), Pfizer (Inst), BeiGene (Inst), Rubius Therapeutics (Inst), Strategia (Inst) Yi-Bin Chen Consulting or Advisory Role: Magenta Therapeutics, Incyte, Kiadis Pharma, AbbVie, Equillium, Daiichi Sankyo/Lilly, Celularity, Actinium Pharmaceuticals Arthur Kim Consulting or Advisory Role: Kintor Pharmaceutical Patents, Royalties, Other Intellectual Property: Uptodate, Chapter Royalties Aditya Bardia Consulting or Advisory Role: Novartis (Inst), Genentech, Pfizer (Inst), Spectrum Pharmaceuticals, bioTheranostics, Merck, Radius Health (Inst), Immunomedics (Inst), Genentech/Roche (Inst), Innocrin Pharma (Inst), Sanofi, Puma Biotechnology, Daiichi Sankyo/Astra Zeneca, Foundation Medicine, Philips Research Funding: Genentech (Inst), Novartis (Inst), Pfizer (Inst), Merck (Inst), Sanofi (Inst), Radius Health (Inst), Immunomedics (Inst), AstraZeneca/Daiichi Sankyo (Inst) Open Payments Link: https://openpaymentsdata.cms.gov/physician/523675 A. John Iafrate Stock and Other Ownership Interests: Archer Biosciences Consulting or Advisory Role: Repare Therapeutics, Kinnate Biopharma, Oncoclinicas Brasil, PAIGE.AI Patents, Royalties, Other Intellectual Property: ArcherDx exclusive license to AMP technology Justin F. Gainor This author is a member of the JCO Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Employment: Ironwood Pharmaceuticals (I) Stock and Other Ownership Interests: Ironwood Pharmaceuticals (I) Honoraria: Merck, Incyte, ARIAD, Novartis, Pfizer, Takeda Consulting or Advisory Role: Genentech, Bristol Myers Squibb, Theravance, Loxo, Takeda, Array BioPharma, Amgen, Merck, Agios, Regeneron, Oncorus, Jounce Therapeutics, Blueprint Medicines, Gilead Sciences, Lilly, Moderna Therapeutics Research Funding: Genentech, ARIAD, Merck, Novartis, Bristol Myers Squibb, Adaptimmune, AstraZeneca, Jounce Therapeutics, Blueprint Medicines, Moderna Therapeutics, Tesaro, Alexo Therapeutics, Array BioPharma No other potential conflicts of interest were reported.