Study: Antibody Response Varies by Tumor Type and Treatment

The studies were published recently in the peer-reviewed journals Cancer Research and Annals of Oncology.

Although immune responses to vaccines appear to be robust for up to six months and breakthrough infections are uncommon in healthy people, the immune response and incidence of breakthrough infections among patients who concurrently undergo cancer treatments have been unclear, said epidemiologist Jane C. Figueiredo, PhD, director of Community and Population Health Research at Cedars-Sinai Cancer.

Furthermore, recent novel COVID-19 variants—with higher transmission rates and reduced antibody sensitivity—increase the risk of infection in cancer patients, adding to the urgency for new insights into vaccination impacts on cancer patients, added Figueiredo, co-lead author of both studies, with Karen L. Reckamp, MD, and Akil A. Merchant, MD.

At the outset of the pandemic, when studies and information about COVID-19 vaccines for cancer patients were limited, many oncologists advised their patients to get vaccinations as soon as they were available because of their higher risk for infection, Figueiredo said.

Observational studies subsequently revealed that Pfizer-BioNTech and Moderna vaccines produce less of an antibody response in cancer patients than in healthy people, said Figueiredo, a professor of Medicine. In fact, patients with certain blood cancers, and those receiving anticancer treatments such as chemotherapy and immunotherapy, may have low or no antibody response after vaccination.

The Cedars-Sinai study published in Cancer Research is significant "because of its important implications for vaccine booster timing and the selection of patients for boosters," Figueiredo said. “Our goal was to provide additional evidence on vaccine response for physicians and patients."

The researchers enrolled cancer patients who donated blood for COVID-19 antibody testing, including 291 patients who were vaccinated with two doses of Pfizer-BioNTech or Moderna vaccines, and 54 who were unvaccinated. Antibody levels and the frequency of breakthrough infections were evaluated by tumor type and the timing of treatment relative to vaccination.

Unvaccinated patients mostly were younger, female, and self-identified as a non-white minority; all of them had blood cancers. Among the cancer patients, the frequency of COVID-19 infection at the time of enrollment was lower in vaccinated patients than their unvaccinated counterparts, the study revealed.

The researchers found that after two doses of the Pfizer-BioNTech or Moderna vaccine, the antibody levels were lower in cancer patients, compared to those without cancer. Patients who received the Moderna vaccine had a higher level of antibodies than those who got the Pfizer-BioNTech vaccine.

"The differences in antibody responses were explained in part by the different treatment regimens," Figueiredo explained. "Responses also varied by the timing between vaccination and anticancer treatment, which vaccine they got, and the patient’s age and ethnicity."

Follow-up analysis a median 42 days after patients received their second vaccine doses showed that antibody levels were higher in patients who were younger, Hispanic, had solid tumors, were undergoing surveillance, or were on hormonal therapies. Four to six months after their second vaccine doses, Hispanic patients still had higher antibody counts than the other participants. The levels also remained higher in younger patients who were not on active anticancer treatments, the study showed.

Breakthrough infections causing severe COVID-19 illness and hospitalization were rare up to six months post-vaccine and occurred only in patients with blood cancers.

One of the outstanding questions is the timing of vaccinations or boosters for patients undergoing immunotherapy, Figueiredo said. Some physicians delay cancer treatment to provide a window for vaccinations, while others delay the shots until treatment is complete to ensure a robust vaccine response.

The Cedars-Sinai study revealed that patients treated with immune therapy before getting a vaccination had a lower antibody response than those who received treatment post-vaccination.

Nevertheless, "there currently is too little data to help with timing decisions," Figueiredo said. "Additional, larger studies examining vaccine immune responses in patients getting immunotherapy, for example, are urgently needed. Tailoring the sequencing and timing of vaccinations may help provide improved immune responses."

The study published in Annals of Oncology provided insight into adverse vaccine reactions and hesitancy in cancer patients.

The study was composed of 128 patients with solid tumors and 80 with blood cancers, most of whom were undergoing one or more cancer treatments. The study found that adverse reactions to vaccinations, such as fever, fatigue and malaise, were common in cancer patients. Women were more likely than men to experience pain and fatigue. Patients with solid tumors reported more symptoms than those with blood cancers, and post-vaccination adverse reactions varied by tumor type and treatment. The study also found that women were more vaccine hesitant than men.

"Cancer patients have a serious condition, and I understand why they may delay being vaccinated," Figueiredo said. "There is a good reason to get vaccinated, and there is cause to pause, too. But overall, vaccines are saving lives and preventing many from experiencing severe disease."

Funding: Research for the study published in Cancer Research was supported by National Cancer Institute award U54CA260591; NIH award P01DK046763; NIH award U01DK062413; NIH award K23H153888; Cedars-Sinai Medical Center; the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute; the Erika J. Glazer Family Foundation; and the Leona M. and Harry B. Helmsley Charitable Trust.

Research for the study published in Annals of Oncology was supported by National Cancer Institute grant award U54CA260591.

Disclosures: Among the co-authors, Karen Reckamp holds a consultant or advisory role at Amgen, AstraZenecca, Blueprint, Boehringer Ingelheim, Daiichi Sankyo, EMD Soreno, Genentech, GSK, Janssen, Lily, Merck KGA, Mirati, Seattle Genetics, Takeda. A full list of disclosures is listed in the study.