Disclosures: Chemaly, Pergam, Shadman and Teoh report no relevant financial disclosures.
July 21, 2021
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Immunization in cancer survivors: Optimizing response, minimizing risk

Disclosures: Chemaly, Pergam, Shadman and Teoh report no relevant financial disclosures.
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The COVID-19 pandemic has underscored the importance of vaccination, both in terms of protecting individuals from infection and eradicating threats to public health.

Cancer survivors who have completed treatment may have compromised immune systems, either for the short term or as part of ongoing immunosuppressive treatment. For this reason, protection from infectious diseases is essential for this population.

However, the immune system impairment these survivors experience may diminish vaccine efficacy or potentially pose further risk.

Steven Pergam, MD, MPH
Steven Pergam

“Anyone who goes through cancer therapy who is on high-risk immunosuppressive therapy will have a higher risk [for] developing infections,” Steven Pergam, MD, MPH, associate professor of the vaccine and infectious disease division at Fred Hutchinson Cancer Research Center and infection prevention director at Seattle Cancer Care Alliance, said in an interview with Healio. “The reason that these patients face higher risk [for] infection is the same reason that some of these patients are not as responsive to these vaccines. The immune system is key for both.”

Severe influenza outcomes

According to a 2020 study by Carreira and colleagues, published in EClinicalMedicine, cancer survivors demonstrated increased risk for complications from influenza compared with those who had not been treated for cancer.

In the population-based cohort study, researchers from London School of Hygiene & Tropical Medicine assessed medical records of over 630,000 individuals in the U.K., more than 100,000 of whom were survivors of various cancers.

The researchers compared rates of influenza hospitalization and death between cancer survivors and those in the control population. They found that compared with those who had no history of cancer, survivors of lymphoma, leukemia and multiple myeloma had a more than 15 times higher risk for severe influenza outcomes (HR = 15.17; 95% CI, 7.84-29.35). Notably, this increased risk continued for at least 10 years after cancer diagnosis (HR = 10.06; 95% CI, 2.47-40.93).

Survivors of other cancer types had more than twice the risk for hospitalization and death for up to 5 years after diagnosis (HR = 2.22; 95% CI, 1.31-3.74).

These findings remained significant even after adjusting for other suspected risk factors such as old age, smoking, socioeconomic status, BMI and other illnesses.

Roy F. Chemaly, MD, MPH, FACP, FIDSA
Roy F. Chemaly

“Survivors should absolutely be up to date on the flu vaccine,” Roy F. Chemaly, MD, MPH, FACP, FIDSA, professor of medicine, chief infection control officer and director of clinical virology at The University of Texas MD Anderson Cancer Center, said in an interview with Healio. “They are no longer on active treatment, and so they should respond better than our [patients with cancer] on treatment.”

According to Pergam, influenza vaccination ideally should be given during periods of seasonal influenza emergence in the community.

“We try to vaccinate these individuals as quickly as possible within that time frame,” Pergam said. “However, we also try to balance that with a time frame that’s going to be most beneficial to them.”

It is generally recommended that all family members and caregivers of immunocompromised individuals also receive the influenza vaccine, Chemaly said.

“We always recommend for family members, caregivers and those in contact with our immunocompromised patients to get vaccinated so they can protect their loved ones,” he said. “However, we recommend that they get the killed virus and not the live attenuated virus.”

Blood cancer survivors

Although some degree of immune system impairment may occur among survivors of any cancer, this effect may be ongoing in survivors of blood cancers due to chronic immunosuppressive treatments they receive.

Mazyar Shadman, MD, MPH
Mazyar Shadman

“Patients with blood cancers have an immune system that is not normal; they’re immunocompromised not just from the disease, but also from the treatments we give them, which suppress the immune system,” Mazyar Shadman, MD, MPH, associate professor in the clinical research division at Fred Hutchinson Cancer Research Center, said in an interview with Healio. “It’s more of a problem in survivors of blood cancers like leukemia, lymphoma and myeloma, and those who undergo stem cell transplant.”

Shadman said when planning a treatment regimen for a patient with blood cancer, he generally makes sure the patient is vaccinated beforehand. The timing might vary depending on the type of vaccine, but Shadman said patients usually are vaccinated between 2 and 4 weeks prior to treatment. In the case of some treatments, patients are revaccinated after completing the regimen, he said.

“Depending on the type of treatment they’re getting, we wait until their immune system recovers from that treatment,” he said. “Then revaccination happens later. For stem cell transplant, for example, we usually revaccinate somewhere between 6 months to a year after transplant.”

Survivors who have been treated with chemotherapy or other regimens may be vaccinated after treatment, but only if they were not vaccinated before treatment.

“If they had the vaccine before starting treatment, you don’t necessarily have to repeat it,” he said. “The exception is for stem cell transplant, because it changes the immune system.”

In the case of the COVID-19 vaccine, research has shown that immune response can be impacted substantially by certain types of blood cancer treatment.

“For example, we’ve seen that monoclonal antibodies that target CD20 to treat [chronic lymphocytic leukemia] are associated with extremely low response to the vaccine; lymphoma treatment in general has a very negative impact on response,” Shadman said.

A 2021 systematic review and meta-analysis by Vijenthira and colleagues showed low seroconversion rates to COVID-19 vaccination among patients undergoing active anti-CD20 therapy. According to the researchers, “the low response rate of patients on anti-CD20 therapy appears to be largely attributable to the anti-CD20 therapy rather than the disease or other treatments, and response to vaccination seems to improve incrementally over time but may not reach the level of healthy controls even 12 months after therapy.”

Shadman said given this information, survivors of lymphoma who underwent these treatments should take a cautious approach in terms of COVID-19 prevention measures.

“The implication for patients is that they need to be careful, and not just assume that they’re protected, especially if they’re getting active lymphoma treatment or they have a recent exposure to these treatments,” he said.

‘Prime-boost’ strategies

Pergam, who participated in development of National Comprehensive Cancer Network guidelines related to COVID-19 vaccination, said no “one-size-fits-all” approach exists for patients undergoing cancer treatment and survivors.

“Cancer is quite diverse; there are patients who get therapies that aren’t as immunosuppressive,” he said. “As an example, a woman who has breast cancer and is receiving hormonal therapy is not going to be the same as a patient with leukemia. What we try to do is target periods of time when these patients have the best opportunities to respond to vaccines, and balance that with the period of time when the risk is highest.”

Currently, he said, the NCCN guidelines advise offering the COVID-19 vaccine to survivors of blood cancers at 3 months after transplant. For these and other patients who are highly immune suppressed, they recommend a “prime-boost” strategy of one dose to prime the immune system and a subsequent boost. However, he emphasized “patients should get whatever vaccine is available.”

“For some patients, a single dose of something like the Johnson & Johnson vaccine is probably fine, but in other patients who are highly immune suppressed, we prefer this prime-boost strategy,” Pergam said. “The challenge now is understanding if an additional booster vaccination is beneficial (a third dose). There are a few papers looking at this in other populations with some benefits.”

Pergam added that well-designed and well-conducted trials are needed to better understand how to best employ additional boosters.

“This is for two reasons; one is that we don’t know whether there might be risk associated with that additional vaccine,” he said. “And, we’re not sure about what is the best vaccine combination, or whether getting the same vaccine is best. Is it better to have a [messenger RNA] vaccine followed by something like an adenovirus vector vaccine, such as the Johnson & Johnson vaccine? Or is it the other way around? We just don’t know. No doubt, there is going to be a lot of emerging science in this space over the year.”

Encouraging HPV vaccine uptake

Cancer survivors are especially in need of HPV vaccination, according to Deanna Teoh, MD, MS, assistant professor in the department of obstetrics, gynecology and women’s health at University of Minnesota Medical School.

Deanna Teoh, MD, MS
Deanna Teoh

“In general, in the U.S. population, HPV vaccination has always lagged behind our goals for various reasons, but it’s even lower in young cancer survivors,” Teoh said in an interview with Healio. “This is a concern, because individuals with a history of pediatric cancers have a three to four times increased risk for either precancerous changes or cancer of the cervix.”

She said although this presents a clear concern for biologic females in terms of developing cervical cancer, the full implications for biologic males with previous pediatric cancers are not entirely less defined, but of emerging importance.

“We don’t have as much of a measure of the impact of HPV vaccination for males, because we do not have any screening strategies for HPV-associated cancers for which males are at risk,” she said. HPV-associated head and neck cancers are the most prevalent HPV-associated cancers, especially among males.”

Teoh said gaps in the continuity of survivorship care may partly account for the low uptake of HPV vaccination among survivors.

“Unfortunately, even in dedicated survivorship clinics, there are so many issues that need to be addressed; there are many things that these young cancer survivors are at risk for,” she said. “Also, primary care providers are used to recommending the vaccine for patients [aged between 9 and 12 years], but if a patient is getting cancer treatments at that time and is not eligible for the vaccine, that may be a missed window. If the primary care provider sees them in their late teens, it might not be on their radar to recommend the vaccine.”

Teoh said she and her colleagues have received funding from the Defense Department to evaluate different modes of communication for increasing HPV vaccination in the survivorship population.

“These are patients who have been outside of treatment and without disease for 3 to 5 years,” she said. “It’s definitely safe to give the HPV vaccine at this point, and we will be starting a study this fall on how we can best educate patients on the importance of the vaccine, incorporate HPV vaccination into survivorship recommendations and facilitate getting the vaccine.”

References:

For more information:

Roy F. Chemaly, MD, MPH, FACP, FIDSA, can be reached at rfchemaly@mdanderson.org.

Steven Pergam, MD, MPH, can be reached at spergam@fredhutch.org.

Mazyar Shadman, MD, MPH, can be reached at mshadman@fredhutch.org.

Deanna Teoh, MD, can be reached at dkteoh@umn.edu.