Steven Pergam, MD, MPH, Discusses NCCN’s “Strong Preference” for mRNA Vaccines in Patients With Cancer to Prevent COVID-19

The National Comprehensive Cancer Network (NCCN) announced significant updates to its expert consensus recommendations on vaccination and prevention of COVID-19 in people with cancer on January 4, listing a preference for mRNA-based vaccines and calling for patients and caregivers alike to receive boosters.¹

A statement from NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis said that the panel “endorses vaccination for all eligible persons based on FDA-approved indications or emergency use authorization” and emphasized the need for everyone to be fully vaccinated—including third doses.

Caregivers and close contacts of persons with cancer should also be fully vaccinated to offer the best possible protection for those who are immunocompromised, the experts recommend. The recommendations call for vaccination among the general public.

Vaccination should be delayed for at least 3 months following hematopoietic cell transplantation or engineered cellular therapy, such as chimeric antigen receptor (CAR) T-cell therapy, to ensure the best possible vaccine efficacy. These are the same recommendations given to the public who have been exposed to COVID-19 or have received recent monoclonal antibody therapy.

While the committee supports any of the possible FDA-approved vaccines, it expressed “strong preference” for the mRNA vaccines—Pfizer/BioNTech, which has full FDA approval in adults, or Moderna.

The committee also “strongly supports mandates for health care worker vaccination.”

“All of us are called to do everything we can to save as many lives as possible during the ongoing pandemic,” Robert W. Carlson, MD, chief executive officer, NCCN, said in a statement.²

“Vaccination is our most effective approach for avoiding serious COVID-19 complications, including hospitalization and death. However, research shows many immunocompromised people develop inadequate immune responses from vaccines,” Carlson said. “Thankfully, we now have additional tools to help people in active treatment for cancer, solid organ transplant recipients, engineered cellular therapy (eg, CAR T-cell) or stem cell transplant recipients (also called hematopoietic stem cells), and those with other immunodeficiency-causing conditions (such as HIV, DiGeorge syndrome, or Wiskott-Aldrich syndrome).”

“We have new agents to prevent and treat COVID-19 that will benefit patients with cancer,” said Brahm Segal, MD, of Roswell Park Comprehensive Cancer Center, a co-leader of the NCCN Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis. “An important challenge on a national level is to ensure drug availability to patients with cancer and others at high risk for COVID-19. The revised recommendations from the NCCN Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis will provide guidance on the use of these agents for patients with cancer, including prioritization when supplies are limited.”

In its statement, the committee said it also supports recommendations from the CDC, the American Society of Transplantation and Cellular Therapy, and the American Society of Hematology (ASH) that previously vaccinated patients completing stem cell transplantation or engineered cellular therapy should receive a repeat vaccination series starting at 3 months post treatment.

Steven Pergam, MD, MPH, director of infection prevention at Seattle Cancer Care Alliance and infectious disease physician at Fred Hutchinson Cancer Research Center, serves as a co-leader for the NCCN Advisory Committee on Covid-19 Vaccination and Pre-exposure Prophylaxis. Pergam spoke with Evidence-Based Oncology™ (EBO) on the day the update was released about the evolution of NCCN’s recommendations and key takeaways from the update.

EBO: What are the most important takeaways from NCCN’s update on COVID-19 vaccines and prevention?

Pergam: Things change quite a bit, and we hadn’t had an update in a little while. [We] specifically addressed some of the vaccine changes that have come along in the past few months. One is a recommendation for an additional booster after the Johnson & Johnson vaccine. We made some updates specifically to address that. We also addressed some questions around antibody testing, and whether to test patients for antibodies who are going through the vaccine process. We updated the new recommendations for children to get vaccinated in the lower age ranges. We [also] discussed [the] important [issue of the] mix-and-match approach that was approved by the FDA and others, where you don’t necessarily have to get the same vaccine [for a booster]. We really were encouraging people to make sure that they’re getting vaccinated and, if they had received the Johnson & Johnson or Pfizer, that it was possible to get [a different] vaccine to complete your series.

Finally, the biggest news [from the CDC] was that the mRNA vaccines are the primary selection, and that’s primarily what we’re recommending as the first choice if possible. The new addition was related to monoclonal antibody prevention, which is a new drug called Evusheld, made by AstraZeneca. It’s a prophylaxis agent, so it’s given for preexposure prophylaxis in high-risk immunosuppressed patients. That’s a drug that’s like other monoclonals that have been given for treatment, but instead, it has a longer half-life—at least it’s reported to have a longer half-life. Patients who might not respond as well to vaccines [can get this] and are probably more protected against COVID-19 during that period after dosing. We made some specific recommendations about groups who should be targeted for that particular therapy, and that’s consistent with the [National Institutes of Health] guidelines that were recently published.

EBO: From your vantage point in Seattle, you have seen the trajectory of COVID-19 and cancer from the very start of the pandemic. Have any major recommendations evolved or shifted since the beginning?

Pergam: Being on the forefront of this was kind of challenging at the beginning. I think what you’ve seen is that people really work together to try to protect patients as best as possible. We’ve gone from little masking in the community to masking in the community and masking in health care institutions. We’ve seen a shift from having no therapies available to now therapies being available. We’ve had a shift from no vaccines to vaccines. I think the biggest shift right now is just the number of people who are getting infected; Omicron’s ability to transmit is quite a big shift.

Despite being engaged in this very early, I think we [are nonetheless surprised at] the number of patients who we’re seeing who are coming up positive now, just because it’s so much more prevalent. We are in a different situation, though, because we do have some treatments available, and we have people who are vaccinated. So, I think in general, patients are a little more protected than they were during the initial phase [of the pandemic]. I think people are also being more cautious. I think they’ve learned a lot through the process: They know to wear masks in public; they’re more cautious when they go out in group activities. I think our cancer patients are more aware, as are our providers about providing that advice.

EBO: Just before the Pfizer vaccine received its Emergency Use Authorization, the director of the National Institute of Allergy and Infectious Diseases, Anthony Fauci, MD, recommended at the American Society of Hematology meeting in December 2020 that patients with blood cancers get vaccinated.³ He said that even if the vaccine was not fully effective, some protection was better than none. Is that advice still basically true?

Pergam: Understanding exactly how vaccines work in an immunosuppressed population, [with] cancer patients being one of those, is still really complex. We know that we use antibody levels and antibody responses to vaccine as a surrogate marker for protection. But other aspects of the immune system are harder to assess—things like T-cell immunity—that also probably play important roles, so even people who don’t have full antibody responses may have some level of protection. [As] I try to explain to patients, you don’t want to meet COVID on the street unless you’ve been vaccinated first, because that’s going to give you some protection. Even if it’s a small percent—if it gives you protection of, say, 10%—it’s better than going into that meeting not protected at all. So, vaccines are important. What has shifted is now we’re doing more aggressive vaccines. Instead of doing 2 doses, we’re doing 3 doses as the primary, with a boost about 6 months later. I think that boost is important and can provide additional protection. Immunosuppressed patients have a lot of opportunities to get additional benefits from vaccines. They’re not perfect, and you still need to think about other things that you can do to protect yourself, but I absolutely agree that vaccine remains the most important prevention method we have as a primary, and then those others are just as critical—the masking, social distancing, etc.

EBO: The NCCN preference for mRNA vaccines aligns with data presented in December 2021 by the Leukemia and Lymphoma Society at the ASH meeting in Atlanta. Can you discuss why the mRNA vaccines offer better protection for these patients?

Pergam: I can’t speak to why it’s better. [There are always] nuances of how these vaccines work and the specifics about [how they work in] particular populations, and the [mRNA vaccine], this particular approach, does seem to be a particularly powerful method for delivering [protection against] COVID. [This is] how it works basically: These are coated in a lipid particle with an mRNA component in it that basically connects and goes into a cell. The mRNA goes into the cell; the mRNA then transcribes the mRNA components and makes it into a protein production in the cell, and that protein is the spike protein that’s put onto the surface of the cell. It doesn’t actually cause infection…but it allows the immune system to create a response to that spike protein, and that has the ability to create an immune response, which is what we need to be prepared for the next time it sees that.

The way it’s been described by some people, it’s like a “Wanted” poster: It’s there, you see it, and then it disappears, but everyone remembers what was on that poster. On that spike protein, that immune system is now ready for that individual when it comes through.

The adenovirus vectors are a little bit different. They use a similar process to get information in, but a viral vector uses that same mechanism instead of doing it through that lipid particle. They’re a little bit different in how they work. It’s unclear exactly—I can’t speak to why one is necessarily better than the other—but definitely the mRNA vaccines appear to have a more robust immune response, at least by antibody levels, particularly, within the immunosuppressive population. Now, there may be some advantages to adenovirus vaccines—there may be some more longer-term T-cell responses—but I think we’re going to need to continue to study this and understand how they each work and where specific niches may work better than others.

EBO: Can you discuss the NCCN recommendations for patients receiving CAR T-cell therapy?

Pergam: If people are getting CAR T-cell therapy or [bone marrow transplant] therapy, you’re sort of replacing or really updating their immune system; so, even if they’ve been previously vaccinated with a full series, they need to be revaccinated post [procedure]. [In other words], with an allogeneic transplant, you’re providing a whole new immune system, and a lot of those [previous] memory cells are gone; therefore, you need to reeducate the system….We’re revaccinating all those patients post those events because of the way the therapy affects the immune system in general, and that has been a big update, I think, in this time frame. We’re waiting typically about 3 months post therapy, because we want that cellular recovery to be back and then vaccinate them at that time. 

REFERENCES

1. NCCN. Recommendations of the National Comprehensive Cancer Network (NCCN) Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, version 5.0. January 4, 2022. Accessed January 9, 2022. https://www.nccn.org/docs/default-source/covid-19/2021_covid-19_vaccination_guidance_v5-0.pdf?sfvrsn=b483da2b_74

2. Darwin R. Protecting people with cancer from COVID-19: new recommendations from cancer guidelines organization. News release. National Comprehensive Cancer Network; January 4, 2022. Accessed January 9, 2022. https://www.nccn.org/home/news/newsdetails?NewsId=3053.

3. Caffrey M. Taking immunosuppressants? Fauci says get the COVID-19 vaccine. American Journal of Managed Care®. December 6, 2020. Accessed January 9, 2022. https://www.ajmc.com/view/taking-immunosuppressants-fauci-says-get-the-covid-19-vaccine