A study by researchers in the United States and Switzerland, funded in part by a National Cancer Institute grant to the Mays Cancer Center and a grant from the American Cancer Society and the Hope Foundation for Cancer Research, demonstrated that nearly all patients with cancer developed a good immune response to the SARS-CoV-2 (COVID-19) mRNA vaccines three to four weeks after receiving their second dose, but the fact that a small group of the patients exhibited no response raised questions about how their protection against the virus will be addressed moving forward.

To evaluate the efficacy of the vaccine in patients diagnosed with cancer, the researchers used a prospective cohort to assess the seroconversion rates and the ant-SARS-Cov-2 spike protein antibody titers following the 1st and 2nd dose of either the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines.

COVID-19 vaccine. Photo Courtesy: U.S. Air Force photo by Senior Airman Eugene Oliver.

Among the 131 patients studied between January and April 2021, 94% achieved seroconversion and developed antibodies to the coronavirus.

The researchers found that seroconversion and antibody titers were significantly lower in patients diagnosed with hematological malignancies compared to patients diagnosed with solid tumors (77% versus 98%, p = 0.002).

A total of seven high-risk patients did not develop an antibody response. “We could not find any antibodies against the virus in those patients,” said Dimpy P. Shah, MD, Ph.D., of the Mays Cancer Center, home to UT Health San Antonio MD Anderson.

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The results of the study are important for public health decision-making.

“[These results have] implications for the future. Should we provide a third dose of vaccine after cancer therapy has completed in certain high-risk patients?” commented Shah, who is a corresponding author of the study, which was published in the journal Cancer Cell. Coauthors are from the Mays Cancer Center and the University of Geneva.

“With other vaccines and infections, patients with cancer have been shown not to develop as robust an immune response as the general population,” said study senior co-author Ruben Mesa, MD, FACP, executive director of the Mays Cancer Center.

“It made sense, therefore, to hypothesize that certain high-risk groups of patients do not have antibody response to COVID-19 vaccine,” Mesa added.

“Patients with hematological malignancies, such as myeloma and Hodgkin lymphoma, were less likely to respond to vaccination than those with solid tumors,” said Pankil K. Shah, MD, Ph.D., of the Mays Cancer Center, who served as co-lead author of the study with Alfredo Addeo, MD, senior oncologist at the Geneva University Hospital.

Among the high-risk groups, patients receiving a therapy called Rituximab within six months of vaccination developed no antibodies. Rituximab is a monoclonal antibody used in the treatment of hematological cancers and autoimmune diseases.

Patients on chemotherapy that is toxic to cells developed antibody response, but it was muted compared to the general population. “How that relates to protection against COVID-19, we don’t know yet,” Dimpy Shah noted.

Delta variant
The Delta variant, also known as B.1.617.2 and belongs to a viral lineage first identified in India during a ferocious wave of infections there in April and May, and other mutants of the COVID-19 virus were not examined in the study.

The Delta variant is moderately resistant to vaccines, particularly in people who have received just a single dose. A Public Health England study published on 22 May found that a single dose of either AstraZeneca’s or Pfizer’s vaccine reduced a person’s risk of developing COVID-19 symptoms caused by the Delta variant by 33%, compared to 50% for the Alpha variant. A second dose of the AstraZeneca vaccine boosted protection against Delta to 60% (compared to 66% against Alpha), while two doses of Pfizer’s jab were 88% effective (compared to 93% against Alpha).  However, the effect of these variants has not been studied yet.

The researchers also did not analyze the response of infection-fighting T cells and B cells in patients with cancer.

Study design
The median age of patients in the study was 63. Most of the patients (106) had solid cancers as opposed to hematological malignancies (25). The study population was 80% non-Hispanic white, 18% Hispanic, and 2% Black.

“We recommend that future studies be done in Black, Asian and Hispanic patients, as well, to see if there are any differences in vaccination immune response,” Mesa said.

“In countries where there is lack of vaccination, there is talk that one dose might confer adequate protection, but this may not be true in the case of patients with cancer,” Dimpy Shah added.

“We observed a significant difference in response when two doses were given,” Shah further noted. “At least for patients with cancer, two doses are very important for robust antibody response.”

Unique study
Pankil Shah explained that the study is unique because, unlike a few studies conducted in the past that evaluated immune response on the day of the second dose or within seven days of it, this study waited three to four weeks to obtain results.

Patients with high-risk cancers, especially those receiving anti-CD20 antibodies, should continue to take precautions even after being vaccinated, the study implies. “They still need to have that awareness that they could potentially be at risk because their body has not responded to vaccination,” Pankil Shah concluded.

Highlights of prescribing information
Rituximab (Retuxan®; Genentech/Roche)[Prescribing Information]

Emergency authorization
Pfizer-BioNTech Covid-19 Vaccine Emergency Use Authorization Combined Full Prescribing Information and Fact Sheet. BNT162b2
Moderna Covid-19 Vaccine Emergency Use Authorization Combined Full Prescribing Information and Fact Sheet. mRNA-1273

Reference
[1] Addeo A, Shah PK, Bordry N, Hudson RD, Albracht B, Di Marco M, Kaklamani V, Dietrich PY, Taylor BS, et al. Immunogenicity of SARS-CoV-2 messenger RNA Vaccines in Patients with Cancer First published: June 18, 2021, Cancer Cell; doi.org/10.1016/j.ccell.2021.06.009

 

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