Most patients with solid tumors develop antibodies after COVID-19 vaccination, but many patients with hematologic malignancies fail to seroconvert, according to a meta-analysis published in the European Journal of Cancer.1

The research also showed a low risk of breakthrough SARS-CoV-2 infection among cancer patients overall — less than 1%. However, cancer patients were about twice as likely as non-cancer control individuals to have a breakthrough infection after being fully vaccinated.

The meta-analysis included 35 studies that encompassed more than 8000 cancer patients in the United States, Europe, Israel, and Turkey. Most patients received the Pfizer-BioNTech COVID-19 vaccine.

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The studies, which were published between March 2020 and August 2021, reported seroconversion rates based on levels of anti-spike (anti-S) protein antibodies. Researchers also analyzed data on T-cell response and rates of SARS-CoV-2 infection after vaccination from the 6 and 14 studies, respectively, that reported these endpoints.

It is the first meta-analysis of the immune response to COVID-19 vaccination in the cancer patient population.

“Patients with cancer were not included in the main Pfizer and Moderna [COVID-19 vaccine] trials, or they were underrepresented, so you cannot draw conclusions from those,” said Bryan Vaca-Cartagena, MD, a physician at Hospital Zambrano Hellion Tecsalud in Mexico and an author of the meta-analysis. “When you do a meta-analysis, you are gathering all the findings from small studies…, and then you can get a solid conclusion that, I think, can resemble a big, randomized controlled trial.”

The meta-analysis results support the effectiveness of these vaccines, Dr Vaca-Cartagena said. He and his colleagues decided to perform the meta-analysis after conducting a survey that revealed vaccine hesitancy among patients with breast cancer in Mexico.2

Seroconversion by Cancer Type, Immunization Status

The meta-analysis showed that patients with solid tumors had consistently high rates of seroconversion after complete immunization — 94% across all the studies analyzed.1 However, 53% of solid tumor patients produced anti-S antibodies after incomplete immunization.

Among patients with a hematologic malignancy, there was a wide range in seroconversion rates across the studies. Overall, 65% of patients developed anti-S antibodies after complete immunization, and 49% developed anti-S antibodies after partial immunization.

When compared with non-cancer control individuals, patients with hematologic malignancies were 37% less likely to seroconvert after being fully immunized and 57% less likely to seroconvert after partial immunization.

Solid tumor patients had a 5% lower likelihood of seroconversion after full immunization, when compared with non-cancer control individuals. However, the cancer patients had a 55% lower likelihood of seroconversion after partial immunization.

“One of the most important findings was about the importance of completing the vaccination scheme. Even though it was not the same efficacy as in non-cancer patients, we proved that [vaccines] were efficacious and reduced the risk of getting infected with COVID-19,” said lead study author Andrea Becerril-Gaitan, MD, a physician at Hospital Zambrano Hellion Tecsalud.

The researchers were not able to assess the effects of cancer treatments on immune response to vaccination because there was not enough data across the studies included. Likewise, the researchers were not able to investigate whether certain types of solid and blood cancers were associated with lower rates of seroconversion.

“Many more studies have come out now,” and the group may consider doing another meta-analysis in a few months, said study author Ana Ferrigno, MD, also from Hospital Zambrano Hellion Tecsalud.

Defining Protection

One of the big unanswered questions is what level of anti-S antibodies is needed to protect patients from SARS-CoV-2 infection. Each study included in the meta-analysis set a threshold antibody level above which participants were considered seroconverted or seropositive.

“That is a very blunt metric because what we are calling positive right now is relatively arbitrary,” said Joshua Hill, MD, an assistant professor in the vaccine and infectious disease division at Fred Hutchinson Cancer Research Center in Seattle, who was not involved in the meta-analysis.

Patients with hematologic malignancies may be just above the threshold but still have lower antibody titers than healthy individuals, and “that does probably modulate your risk of getting infected,” Dr Hill noted.

Recent studies have started to put numbers on the exact level of anti-S antibodies that correlate with protection from symptomatic SARS-CoV-2 infection in people who received the Moderna COVID-19 vaccine, as well as the AstraZeneca vaccine.3,4

Although fewer studies have examined T-cell response, the meta-analysis showed that 60% of cancer patients mounted a T-cell response after complete vaccination.1

Another recent study showed T-cell responses among 26% (28/108) of patients with a hematologic cancer who did not seroconvert after full immunization.5 On the other hand, 7% (1/14) of patients with a solid tumor who were seronegative mounted a T-cell response.

“We do not know how much the seronegative patients are protected by a T-cell response,” Dr Ferrigno noted.

Low Risk of Breakthrough Infection?

Despite lower seroconversion rates, particularly among patients with hematologic malignancies, the meta-analysis showed that patients with cancer had a 0.55% likelihood of SARS-CoV-2 infection after full or partial immunization.1  

“These low numbers actually show that vaccines are working, even in cancer patients,” Dr Vaca-Cartagena said.

However, the authors also noted many reasons why this finding may not necessarily represent breakthrough infection rates in the broader cancer patient population. The studies had short follow-up periods in which researchers looked for infections and may have tracked cases before the highly transmissible Delta variant became prevalent or in areas that had low COVID-19 rates in general.

“I would be really cautious about how people interpret [these breakthrough rates] because I think that is underrepresenting the reality,” Dr Hill said. “We really counsel hematologic malignancy patients to get vaccinated but to behave, unfortunately, as if you have not been vaccinated.”

As such, these patients may not be lowering their guard after vaccination as much as healthy adults and patients with solid tumors, which may be keeping the number of breakthrough infections low, he explained.

Furthermore, when compared with healthy control individuals, cancer patients were about 3 times more likely to have a breakthrough infection after partial vaccination (risk ratio [RR], 3.21; 95% CI, 0.35-29.04) and 2 times more likely to have a breakthrough infection after full vaccination (RR, 2.04; 95% CI, 0.38-11.10).1

New Data from Booster Studies

The meta-analysis did not include data on seroconversion rates in cancer patients after a booster dose of a COVID-19 vaccine, which the US Centers for Disease Control and Prevention (CDC) recommends for patients who have been receiving active cancer treatment.6

Since the researchers conducted the meta-analysis, studies have come out suggesting that additional vaccine doses may benefit patients with cancer.7,8

One small study showed that 56% of patients with hematologic malignancies, including some on active treatment, who were seronegative after full immunization seroconverted after an addition dose.8

That “is very good news and a very good sign that boosters work,” Dr Ferrigno said.

Nevertheless, as the authors wrote, studies have shown that a “substantial proportion” of blood cancer patients who did not produce anti-S antibodies following complete vaccination continue to be seronegative after receiving an additional dose.9 

The fact that some patients have poor immune responses even after 3 vaccine doses highlights the importance of additional precautions to prevent SARS-CoV-2 infection, according to Dr Vaca-Cartagena.

“We should continue to wash hands, use face masks, avoid massive gatherings,” he said. “But also, after doing all these things and being very cautious, if you get infected, now we have some promising therapies; for example, the use of monoclonal antibodies and oral antivirals.”

Disclosures: Dr Hill declared relationships with Gilead Sciences, Allovir, Takeda, and Karius. Dr Vaca-Cartagena, Dr Ferrigno, and Dr Becerril-Gaitan reported having no disclosures. Other authors of the meta-analysis declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

  1. Becerril-Gaitan A, Vaca-Cartagena BF, Ferrigno AS, et al. Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: A systematic review and meta-analysis. Eur J Cancer. 2021;S0959-8049. doi:10.1016/j.ejca.2021.10.014
  2. Villarreal-Garza C, Vaca-Cartagena BF, Becerril-Gaitan A, et al. Attitudes and factors associated with COVID-19 vaccine hesitancy among patients with breast cancer. JAMA Oncol. 2021;7(8):1242-1244. doi:10.1001/jamaoncol.2021.1962
  3. Gilbert PB, Montefiori DC, McDermott AB, et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science. Published online November 23, 2021. doi:10.1126/science.abm3425
  4. Feng S, Phillips DJ, White T, et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. medRxiv. Published online June 24, 2021. doi:https://doi.org/10.1101/2021.06.21.21258528
  5. Ehmsen S, Asmussen A, Jeppesen SS, et al. Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer. Cancer Cell. 2021;39(8):1034-1036. doi:10.1016/j.ccell.2021.07.016
  6. COVID-19 vaccines for moderately to severely immunocompromised people. US Centers for Disease Control and Prevention. Updated November 23, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html   
  7. Shroff RT, Chalasani P, Wei R, et al. Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors. Nat Med. 2021;27(11):2002-2011. doi:10.1038/s41591-021-01542-z
  8. Shapiro LC, Thakkar A, Campbell ST, et al. Efficacy of booster doses in augmenting waning immune responses to COVID-19 vaccine in patients with cancer. Cancer Cell. 2021;S1535-6108(21)00606-1. doi:10.1016/j.ccell.2021.11.006
  9. Re D, Seitz-Polski B, Carles M, et al. Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies. medRxiv. Published online July 22, 2021. doi:https://doi.org/10.1101/2021.07.18.21260669

This article originally appeared on Cancer Therapy Advisor

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Cancer COVID19 COVID19 Vaccine