Solving the Puzzle of Cancer and COVID-19 Vaccination

Cancer seems to put people in harm’s way when it comes to COVID-19. Studies conducted early on in the pandemic — well before the delta variant and now omicron started circulating — strongly suggested that cancer patients were more likely to suffer a severe case of COVID-19.

For that reason and others, public health officials and others see vaccination as being especially important for people with cancer.

“Yes, it is recommended for all cancer patients to get COVID-19 vaccinations as they are at higher risk for poor outcomes if they get infected with COVID-19,” says Richard Parker, M.D., chief medical officer of Arcadia, a healthcare data and population health company
in Boston.

There may, however, be some lingering hesitancy among cancer patients. People with active malignancies were, by and large, excluded from the clinical trials of the vaccine, but there is now wide experience with the vaccines, and no safety issues specific to cancer patients have been seen.

“The main concern about getting the vaccine is not whether it’s safe for people with cancer,” the American Cancer Society says on its website, “but about how effective it will be, especially in people with weakened immune systems.”

Jalal S. Baig, M.D., a medical oncologist at the Cancer Treatment Centers of America in suburban Chicago, says cancer patients who contract COVID-19 may have poorer outcomes. Whether the vaccination generates a robust immune response depends, he says, on how long ago they were in active treatment. “Those who have been off of any cancer treatments like chemotherapy for more than six months are better protected by two vaccine doses,” says Baig. “But patients who are actively receiving chemotherapy generate poorer protection from two doses. A booster shot becomes more important for them.”

There’s evidence to back up what Baig is saying. Results of a study of 131 cancer patients reported in Cancer Cell last year showed that 94% developed a strong antibody response — seroconversion — after being vaccinated with either the Pfizer-BioNTech or the Moderna COVID-19 vaccine. And the Swiss and American research team found no difference in the antibody response between the two vaccines. They did, though, find that patients who had been treated with conventional chemotherapy or monoclonal antibodies within six months before their first vaccine dose had a less robust antibody response.

Especially vulnerable

Louis Potters, M.D., senior vice president and deputy physician-in-chief at Northwell Health Cancer Institute in Lake Success, New York, notes that patients with hematologic cancers such as chronic lymphocytic leukemia (CLL) may not make antibodies against the SARS-CoV-2 virus that causes COVID-19 following vaccination. Those patients are still encouraged to get vaccinated and boosted. Parker makes the same point: “Some patients with hematologic or blood-based cancers such as multiple myeloma and leukemia have a greatly reduced immunological response to the vaccines, meaning that they may not get as much protection as a person with a normal immune system.”

A review article published in European Journal of Cancer late last year included comparisons between people with hematologic cancers and those with solid tumors, such as breast and prostate cancer. The review encompassed 21 studies with a cumulative total of just over 5,000 patients. In the 17 studies that looked at the antibody response to a second dose of the Pfizer or the Moderna vaccine, the response was significantly lower among the patients with hematologic cancers than in those with a solid-tumor cancer. The difference between the patients with solid tumors and people in the control groups was smaller.

But as with patients with other cancers, the antibody response to COVID-19 vaccination among patients with hematologic cancer hinges, in part, on how long ago they were in treatment. Israeli researchers published findings in the journal Blood last year showing that none of the CLL patients treated with rituximab therapy within the previous 12 months had antibody response to the Pfizer vaccine, whereas 46% of those treated with rituximab 12 months ago or longer had an antibody response. Several other studies of CLL found a similar relationship to the timing of the treatment and the antibody response to vaccination.

Multiple myeloma is another hematologic cancer that has been associated with diminished response to COVID-19 vaccination. Researchers at the Icahn School of Medicine at Mount Sinai in New York reported findings last year from a study that included multiple myeloma patients who had been vaccinated with the either the Pfizer or the Moderna vaccine. Of the 260 patients in this part of the analysis, 219 (84%) produced antibodies, but there were also 41 (16%) “nonresponders” with no detectable antibody levels, most of whom were on a treatment known to suppress the immune system.

Potters notes that antibodies are just one arm of the immune response. There’s also cellular immunity, which features T cells that aren’t as specific to a pathogen as antibodies. “Everyone will also express a T-cell response that cannot be measured that offers protection in addition to antibodies, including some cancer patients,” he says.

Bruce Feinberg, D.O., chief medical officer at Cardinal Health Specialty Solutions, says he has seen through research that some hematologic malignancies and their respective therapies will hamper immune response post-vaccination. It is critical that these patients discuss risk avoidance with their doctors. “The truth is that the greatest risk to cancer patients is the same to anyone who is vaccinated: that is, the risk of new variants that might evade vaccine-induced immune response,” he says.

Oncologists are still working out how to manage cancer treatment and vaccination. Some guidelines suggest that patients scheduled for chemotherapy should be vaccinated three weeks before therapy starts or between cycles.

“It is important to talk with your treating physician before receiving the vaccine, as some medications that impact the immune system may need to be held for a period of time around the vaccine administration,” Potters says.

Prominent multiple myeloma experts wrote an opinion piece published in JAMA Oncology in December 2021 that argued strongly for monitoring the antibody levels of multiple myeloma patients in active treatment to keep tabs on their risk of contracting COVID-19. They described multiple myeloma patients as being in double jeopardy: Those who are most likely to have a poor antibody response to vaccination are the same patients who are at highest risk of severe COVID-19.

Understandably, much of the discussion about cancer and COVID-19 vaccination has focused on people in active or very recent treatment because of the well-characterized immunosuppression. The immune systems of people whose cancers have been successfully treated or managed tend to bounce back.

“Once they are in remission, many patients will have some rebound of their underlying immune responses to vaccines,” Parker says. “It is important to again emphasize the need to be vaccinated regardless of where the patient is on their cancer journey, either during treatment or post-treatment. And this includes the need for booster shots with either the Moderna or Pfizer mRNA vaccine.”

Keith Loria is a freelance writer in the Washington, D.C., area.

Peter Wehrwein is managing editor of Managed Healthcare Executive®.