Issue: May 25, 2021
Source:

Pergam SA. Keynote. Presented at: COVID-19 & Cancer Consortium Scientific Retreat (virtual meeting). March 26, 2021.

Disclosures: Pergam reports research funding from Chimerix, Global Life Technologies and Merck. He also reports participation in an NIH-sponsored trial for which Sanofi-Aventis provided vaccines.
March 26, 2021
5 min read
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Speaker: Focusing COVID-19 vaccine research on patients with cancer an ongoing challenge

Issue: May 25, 2021
Source:

Pergam SA. Keynote. Presented at: COVID-19 & Cancer Consortium Scientific Retreat (virtual meeting). March 26, 2021.

Disclosures: Pergam reports research funding from Chimerix, Global Life Technologies and Merck. He also reports participation in an NIH-sponsored trial for which Sanofi-Aventis provided vaccines.
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The lack of patients with cancer in COVID-19 vaccine trials has led to a major gap in data to understand how these vaccines work for this population, according to a keynote address at the COVID-19 & Cancer Consortium Scientific Retreat.

“What frustrates many of us who deal with immunosuppressed patients ... is the delay in [vaccine] trials in patients with cancer,” Steven A. Pergam, MD, MPH, associate professor at Fred Hutchinson Cancer Research Center and member of the FDA Vaccines and Related Biological Products Advisory Committee, said in his virtual presentation during the daylong retreat, hosted by Vanderbilt University Medical Center. “Unlike COVID-19, for which we’ve tried to focus on high-risk populations, particularly those in the BIPOC [Black, Indigenous and people of color] community, many times these studies are not focused on the high-risk populations that we deal with every day. That’s a challenge that we’re going to continue to struggle with when it comes to vaccines.”

Steven A. Pergam, MD, MPH, associate professor at Fred Hutchinson Cancer Research Center

However, researchers can glean data from prior vaccination trials and other immunocompromised groups to inform best practices both for the current pandemic and to ensure the health care community is better prepared against future outbreaks, Pergam said.

“I would love to say that ... how we have delivered vaccines across the country has been smooth and organized, and that patients with cancer have been early on in that list, but that has not been uniformly true,” he said. “Many patients are still clamoring to get vaccine, and we’re not quite at a place where everyone can get it. There are still challenges in how we deliver vaccine, and I hope we can learn from what we did wrong and what we did well in this process.”

‘A perfect storm’

Based on data from other vaccination efforts and expertise in the community, National Comprehensive Cancer Network established guidelines on the timing of vaccination among patients with cancer.

That guidance states patients should wait 3 months before undergoing vaccination following hematopoietic stem cell transplantation or chimeric antigen receptor T-cell therapy and until cellular recovery after undergoing cytotoxic therapy, with all other patient groups recommended to receive the vaccine whenever it’s available and they are eligible.

“Using prior examples like the influenza vaccine, we know that response to vaccination is less robust among patients with cancer and those undergoing transplant, but high-dose vaccines and boosting, more than what is recommended for the standard population, may improve response,” Pergam said. “This is how we’ve built our recommendations on a national level.”

Still, this guidance may not be “very comforting” to clinicians, Pergam added, acknowledging that it remains unclear how effective vaccination will be for some patients, such as those receiving rituximab (Rituxan; Genentech, Biogen) or other novel regimens.

“But, the key for us on this committee was to focus on access,” he said. “We really felt urgency of vaccination and avoiding barriers to getting vaccine to our patients was critical, and the need to really advocate for early vaccination in our cancer and transplant patients. We wanted to get these guidelines out to be able to use them as a tool for advocacy in our patient populations. Although it hasn’t worked perfectly, I’ve seen many states have moved quickly to put some of these patients at the top of the list.”

Trials of Pfizer’s vaccine included 1,395 (3.7% of total study population) patients with cancer — none of whom were on active chemotherapy or were currently immunosuppressed — and Johnson & Johnson’s trial included 226 patients (0.5%), including 79 who were immunocompromised after HSCT, but data from these subgroups haven’t been made available, Pergam said.

Pergam also cited a study conducted in the U.K. of response to COVID-19 vaccination among patients with cancer that showed 59% of patients with solid tumors and only 13% of patients with hematologic malignancies mounted antibodies in response to a first dose. Researchers reported greater than 90% seroconversion and evidence of virus neutralization after boosting among the solid tumor population, with numbers too small to make the same assessment in the hematologic malignancies group.

“Most interesting, which is really critical, is that they did see some interferon gamma- and/or interleukin-2-producing T cells specific for SARS-CoV-2 antigens that appear to be somewhat attenuated in [patients with cancer] but also appeared to be improved by that boost,” he said.

Overall, these data suggest that there is potential benefit to vaccination among immunocompromised patients, although questions remain about the level of protection, how high the boost should be, and what levels of antibodies these patients achieve, Pergam said.

Also, efficacy of vaccination drops over time, which emphasizes the importance of a booster, he added, citing data that show a vaccine with 90% efficacy will drop to 70% effectiveness after about 131 days and to 50% at 221 days after vaccination.

“A concern for patients with cancer is that this is the perfect storm, where antibodies to begin with will be less robust, and that decay will start from a place that is not quite as high, leading to less time when the antibody levels will be considered protective,” he said. “That combination of low antibody levels followed by variants that are more apt to escape and need higher vaccine levels really puts patients at high risk with a less robust response.”

A two-dose vaccination strategy and boosting are going to be critical for this group moving forward, he added.

“There is no question in my mind that boosters will be needed,” Pergam said. “The question is how often, and will we have enough to make that possible?”

The ‘next wave’

Other questions that must be answered in the coming months include whether certain vaccines or combinations of vaccines will be more effective for specific patient populations, whether higher doses improve response to vaccines, and if patients who mount limited antibody response to vaccines are protected, according to Pergam.

“The expectation is that vaccinated patients with cancer will continue to develop COVID-19, become hospitalized and die of SARS-CoV-2, despite vaccination,” he said. “It will probably [occur] less, but we need to be wary of this. Decreased community levels will decrease risk, but [there may be] regression to poor vaccine coverage over the year or next 2 years, as we see more vaccine hesitancy develop.”

Amid this uncertainty, it will be important to vaccinate caregivers and family members of patients with cancer, Pergam said, referring to a “cocoon strategy” in which those are vaccinated for whom there will be known efficacy, with less focus given to vaccinating those for whom it will have an unknown efficacy. He also anticipates yearly vaccination for the general population.

Further, Pergam expects more knowledge to be gained on treatments for COVID-19, including monoclonal antibodies to be used as prophylaxis among high-risk populations.

When looking back to determine how things could have been done differently, it’s also important to acknowledge what’s been done well, Pergam said. For instance, data that show a decline in influenza and other respiratory viruses due to COVID-19 mitigation efforts should inform future campaigns to continue to prevent these illnesses, he said.

“We’ve done such great work, we’ve protected our patients, we’ve done education, we’ve shared protocols, we’ve developed national guidelines quickly, studies have been developed on a shoestring, vaccine delivery systems have been improving, and we’ve really focused on equity among our systems and vaccine allocation to high-risk populations,” he said. “The ‘next wave’ we’re talking about today is in science and research that is really going to help our patients be better treated for COVID-19, and I’m hoping what we’re learning from will help us to protect patients in the future beyond COVID, but for other infections and other complications.”

References:

Khoury DS, et al. medRXiv. 2021;doi:10.1101/2021.03.09.21252641.
Monin-Aldama L, et al. medRxiv. 2021;doi:10.1101/2021.03.17.21253131.

Pergam SA, et al. Keynote. Presented at: COVID-19 & Cancer Consortium Scientific Retreat (virtual meeting). March 26, 2021.