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Sep 9, 2021

Dr. Steve Pergam, associate professor of the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center and the Infection Prevention Director at Seattle Cancer Care Alliance, discusses new guidance from the National Comprehensive Cancer Network’s COVID-19 Vaccination Advisory Committee, regarding a third dose of the Pfizer-BioNTech or the Moderna COVID-19 vaccines for patients with cancer.



Dr. John Sweetenham: Hello, I'm John Sweetenham, associate director of clinical affairs at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center and guest host of the ASCO Daily News Podcast today. The U.S. Food and Drug Administration (FDA) has authorized an additional COVID-19 vaccine dose for people with certain medical conditions who received the Pfizer-BioNTech, or the Moderna COVID-19 vaccines.

Following the FDA'S announcement, the National Comprehensive Cancer Network's COVID-19 Vaccine Advisory Committee released new guidelines regarding the third COVID-19 vaccine doses for people with cancer. Joining me to discuss the booster shots is the committee's co-leader, Dr. Steve Pergam. He is associate professor of the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center and the Infection Prevention Director at Seattle Cancer Care Alliance. Steve, thanks for coming on the podcast today.

Dr. Steve Pergam: Well, thank you so much Dr. Sweetenham. It's an honor to talk to my colleagues from oncology who I work with every day and to speak to patients and others who might be listening, so thanks for having me on.

Dr. John Sweetenham: Great, thank you. Before we start, I should mention that my guest and I have no conflicts of interest relating to the topic today, and full disclosures for all guests on the ASCO Daily News Podcast are available on our transcripts at Steve, can you tell us a little about the groups that should be considered eligible for a third dose of the mRNA COVID-19 vaccines right away based on the latest FDA decision?

Dr. Steve Pergam: Sure, the guidelines from the Centers for Disease Control and Prevention (CDC) and from the ACIP after the approval by the FDA are quite broad, and they include patients who are immunosuppressed by medications, such as steroids, drugs like tacrolimus, and then patients with cancer as well, many of whom are often considered immune-suppressed. It gets into patients with immunodeficiencies, and it really addresses a large group of people who are considered immunosuppressed.

And I think part of the reason the guidance was written that way is defining what is immunocompromised to a level where you're not going to respond well to the vaccine is a little bit complex because immunosuppression is such a broad term. So they've left the guidance pretty broadly worded, and so I think it's important that when we think about what this guidance looks like, it's really about trying to be inclusive and trying to be somewhat specific at the same time, which is a really, really hard balance to go across, if that makes sense.

Dr. John Sweetenham: Sure. For those patients who are immunosuppressed in some way, can you say a little about what the data shows regarding the level of protection that these patients may get from a third dose?

Dr. Steve Pergam: Sure, so first, it's actually a little bit difficult to speak to patients with cancer directly. There's not very much data if at all regarding third doses for patients with cancer. So much of the data that supports these recommendations is focused on data that we understand that second dose, receiving that first primary dose, followed by a booster, which is what is common and what's recommended for mRNA vaccines, suggests that patients who have cancer may not respond well to that two-dose regimen.

And it's varied between different groups. Some groups have much less response. So, a patient receiving rituxan (rituximab), which is the anti-CD20 antibody, clearly do not have adequate responses. As an example, patients who are receiving anti-CD20 antibodies like rituxan (rituximab) clearly do not have good responses versus solid tumor patients, which may have a better response to these vaccines.

But regardless, those with immune suppression appear to have decreased responses overall, and the antibody levels that they receive, that they can maximize too are less than the general public. And so there was data looking at different groups who were immune-suppressed and demonstrating some benefit to boosting. And primarily the data is in and amongst solid organ transplants.

There's actually two papers. There is a paper dealing with solid organ transplant recipients, one from France and another from the University of Toronto. And both of these have shown that despite poor responses after the second dose that additional doses amongst those who have solid organ transplants were improved with a third dose approximately at least 28 days post that second booster.

So, that third dose did provide improvements. And in some of that data, up to 60% of those individuals responded to the third dose, where the first dose was only about 4%, and the second dose only about 40%. So you get about, I would say, somewhere around half of the people that had no response in the solid organ transplant population had a defined response with that extra dose.

So, looking at data from other populations of immune-suppressed individuals who have in trials been given these third doses does suggest that there's improved responses. In addition, in some data they have been able to look at T cell immunity and although T cell immunity can be documented in some that received second doses, there are some suggestions that potentially third doses may also potentially improve that. So I think the immune response appears to be better after a third dose, but there are caveats to that.

Dr. John Sweetenham: That's really interesting, and it provokes me to ask a question, which I guess in some ways is a little off the wall, but it's certainly something that I've already heard from a number of patients with cancer. And that is, if as it appears to be the case that a third dose in these patients can get them somewhere closer to the kind of response you might anticipate in the normal population, do you see any role for a fourth dose looking forward? Appreciating that there are no data, but do you think there might be a role for a fourth dose in some of these patients?

Dr. Steve Pergam: Yeah, well, first, I think it's important to understand that a third dose, it's not a panacea. It is not suggesting a third dose is going to protect all patients with cancer. In fact, many of our patients with cancer are highly immunosuppressed, and a third dose, while it may improve the responses in some, it won't completely improve responses. And of those who do respond, they may have a detectable antibody, but the level of protection that they receive with that extra dose may not be a level that is fully protective against infection.

What's hard is the data that's available right now is we don't know whether that third dose is effective or protective against things like hospitalization and death, which are the outcomes that are the most important. So, I think there's still some gaps in our knowledge. But what we do know is that you need a significant amount of antibody to be protected, and some of the data from the Moderna trial has suggested that you need an antibody level of over 1,000 to really be fully protected. That's what they've determined as a correlate of protection.

And I think most of the patients that we're talking about, while some can get over that level, others may have a harder time reaching that level of protection. So, it's important when you're thinking about antibodies and detecting antibodies that it's important to remind your patients that just because they have any antibody doesn't mean it's necessarily fully protective.

Now I think the question of fourth dose is hard because we don't have any data in this space. And more is better is often a mantra in medicine that sometimes is discussed, but I really encourage before we go down that pathway to just giving a fourth dose because we can. And because now Pfizer is an FDA-approved medication that we have a little more flexibility that I think we really should be doing trials to better understand what that extra dose might do, and are we providing more benefit?

I mean, we've seen this with some drugs is that there is a limit to how much cancer response there is with certain agents before we get into issues like toxicity. While I'm not concerned so much about toxicity with mRNA vaccines, what we don't know is what these multiple doses might do. And there's theoretical concerns where if there's been myocarditis seen in younger adults, someone who's receiving multiple doses of one of these agents who's also received cardiotoxic chemotherapy as an example, there might be a change in risk with additional doses.

So, that's all theoretical. I'm not suggesting that's true. But I think what's really important is if we're going to be going down pathways where we're doing additional doses beyond what is FDA recommended, then I would not recommend that at this point that studies need to be done. We need really robust studies in our patients with cancer to really determine whether additional doses are beneficial.

Dr. John Sweetenham: OK, that's really helpful. Thank you. Just switching gears a little bit, could you say a little bit about the timing recommendations for the third shot in immunocompromised patients? And I wonder whether, particularly based on some of the discussions that were held in the National Comprehensive Cancer Network (NCCN) panel, whether you could comment on the timing for those undergoing stem cell transplantation or CAR T-cell therapy. And perhaps say a little bit about those patients who may be undergoing surgery and the appropriate timing for them.

Dr. Steve Pergam: Yeah, so we hope that most of the patients that we're discussing have already received their two doses of one of the mRNA vaccines. And that for those patients who would be potentially eligible to get a booster, we would encourage getting it as soon as possible.

The caveats to that, of course, are the bone marrow transplant recipients and those who are CAR T-cell recipients. Where we really encourage people to delay any doses of the vaccine to a point where the immune response is more likely, and that tends to be around--from data from other vaccines--tends to be around 3 months post-stem cell transplant or 3 months post-cellular immunotherapy. So that's the time frame, and we definitely recommend that.

And then for patients who are undergoing really aggressive chemotherapy, for those that are patients with acute myeloid leukemia (AML) who are getting myelo-specific treatments, maybe they like to organize for them to have their count recovery before they're given their doses. So, patients who were inpatient actively receiving leukemia therapy as an example, as their counts recover, starting their doses after they've completed their therapy, and their counts have recovered, maybe at the time of discharge would be great to give that booster.

And then with those who are getting surgery, what we don't want to do is give somebody a booster the day before surgery, where they might develop some of the symptoms that can occur with people that got these vaccines, which can be general fatigue, but additionally things like fever, which can occasionally happen in patients who have a really robust immune response. And if you have a fever, it can delay your cancer surgery. So, to think about the idea of planning to get your doses after you've had your surgery and had a bit of time to recover might be best.  Planning your vaccine, at least a week before your surgery would be ideal before getting it immediately prior to a surgical procedure would probably be the best.

Dr. John Sweetenham: Right, and I'm assuming that we'll maintain the same guidance for those patients if they're undergoing some kind of radiological procedure that they should avoid undergoing that imaging.

Dr. Steve Pergam: Correct. Yeah, it's a really important comment that's discussed in the guidance is, if you know you're going to be getting something like a PET scan that will be looking for lymphadenopathy or evidence that you might have tumor in other locations for rescreening or restaging, have a discussion with your team about when it would be appropriate because we have seen with these vaccines, they can lead to enlargement of some lymph nodes on the side where your vaccine has been given.

And there have been some images that many of us have seen where your lymph nodes can light up slightly because of an immune response. And what we don't want people to be worried that they have changes in their cancer treatment.  I think what's important is having that discussion prior to a screening that you're going to have with your team to determine the best time to get that extra dose.

Dr. John Sweetenham: Great, thanks. Another question that we've heard in our own practices quite a lot, and it goes back to the beginning of the pandemic really, when the government was recommending that patients at that time got whatever vaccine they could get. So, for our patients with cancer who may have had the Johnson & Johnson (J&J) vaccine as their initial vaccine, what would be your advice now regarding how we should manage those patients as they look for what, for them, would be a second shot. Should they get an mRNA vaccine at this point or should they wait?

Dr. Steve Pergam: Currently according to FDA approval documents, there is not really a pathway to get an extra dose for patients to receive the Johnson & Johnson. You can, of course, have patients get this through--because the Pfizer vaccine is fully approved, it's possible to offer it through that mechanism. But, generally that the FDA approval components at this point don't suggest doing that.

And I think part of the reason is Johnson & Johnson was a later vaccine, so it was rolled out at a later time frame. So, the timing between when Johnson & Johnson was available to now is less time. And so the thought is that potentially waiting for a additional dose may be important.

And I think what's critical about this is that there is data, there is a study that the Johnson & Johnson trial was approved through a trial called the ENSEMBLE trial. And ENSEMBLE 2, which is a trial, which looks at additional doses of Johnson & Johnson--it's a mechanism similar to how mRNA vaccines are given, where there is a prime boost strategy, is actually nearly finalized. And early reports in the news media--I haven't seen any of the actual data--does suggest that the second dose is quite effective and may improve responses.

So my inclination is that Johnson & Johnson patients may eventually have the option of getting either another Johnson & Johnson preferably, but if not available, could receive an mRNA vaccine. I just don't know the timing of that. So at the moment, what I've been telling patients is to hold tight. And then as soon as we know more and what's available and whether they can get a second Johnson & Johnson dose or if there's further recommendations for additional dosing to just hang tight at the moment.

Dr. John Sweetenham: OK, thanks. Again, just switching gears just a little bit here, one of the other discussions that was held in the NCCN Advisory Committee was around people living in the same house as the immunocompromised. I wanted to just take a moment just to say as a member of that panel how much the group appreciated your leadership and how much I personally learned from listening to you and the other leaders of that group. I think it's been a very engaging conversation.

And the group acted, I think, with your leadership, very quickly to get these recommendations out. And I have to tell you that from our own cancer community and cancer center down in Texas, we were very grateful for the guidance we got from the Committee as a whole and from the leadership in particular.

But just a question about those who are living in the same home as the immunocompromised. Could you say a little bit more about the advice the Advisory Committee had for those folks who are living with patients who are immunocompromised?

Dr. Steve Pergam: Sure. So, first, thank you for that comment. I would just say at first that this committee is a committee that makes decisions together. And it's been a wonderful group who has gotten together and been able to develop guidelines quickly as a group.

As much as you've learned from those who lead the group, I would say we've all learned from the members of the committee. It's been really wonderful to see the cancer community come together to make guidance that can really, I think, help providers and patients. So it's important.

I think, in terms of household members and close contacts and family of patients cancer, this fits into what some would call a cocoon strategy, some would call a ring strategy. Where really what you want to do is you want to protect the people around that patient with cancer. Because with patients with cancer, the biggest risk they have for transmission is from a household member.

You're often not masked at home. You are in much more prolonged contact. You're in a household where you can't necessarily socially distance. You're sharing the same air space. Ventilation in homes is also not the level as it is in clinics and such.

The levels of protection that you get at home are significantly less. And so having someone who is a close contact who's positive is quite risky for our patients. And so what we really recommend is for those who are and live in households of patients with cancer that they get vaccinated because even decreasing a small amount of the potential that they get infected doesn't really protect those around them. I think it's really important that the efforts that are made shouldn't just focus on patients with cancer themselves.

And so when our cancer centers are meeting with patients and they're interacting with caregivers and family members that come with them, those conversations should include efforts to ensure that those around them are vaccinated, because that is likely the most clear pathway for infection of an individual. And that really it really crosses a lot of issues, right?

So, a caregiver of a patient with cancer is the person who's most likely to go out to the pharmacy or out to get groceries or do activities where a patient with cancer who is getting therapy may not feel up to that. The patient with cancer themselves is likely to wear personal protective equipment like masks and to socially distance and be staying home and really go to clinic and other things, but to try to avoid social exposure. So, if we can do everything we can to protect that individual, one of the most important things is to get those vaccinated around them.

And I think it's a really important conversation for patients to have with their loved ones and to include the providers in those conversations to help change their opinions about this. And also, I think it's really important for those who live and work in our communities [and] that it needs to be something that businesses understand and that our friends and families understand beyond the even household itself that all of the people a patient with cancer comes into contact with ideally are vaccinated.

And the way we do that is by vaccinating our community. By vaccinating people in our community, we protect the most vulnerable. And we've seen that with vaccines for things like measles, where it takes 95% of the community to be vaccinated to really protect the most vulnerable, where it's important. So, the more we can get out there and talk about the importance of [the] vaccine in our communities and why it's important for vulnerable patients and to really convince those in close households to get vaccinated, I think we're doing our patients a major service and really can help protect them from developing COVID.

Dr. John Sweetenham: Yeah, thanks for those comments. And you did raise the issue of wearing masks. And do you have any comments to make on some of those other measures which we are still working very hard with our patients and our communities over, such as mask wearing and so on? Could you comment a little on that?

Dr. Steve Pergam: Yeah, so what I tell patients is even if they've received both doses of the primary series of mRNA vaccines or a Johnson & Johnson vaccine, and even if they've received a booster that they should still assume that they're not fully protected. Now, it may be that if they are potentially exposed, their chances of developing COVID-19, and for needing hospitalization and for going on to need ICU admission, et cetera are substantially reduced with [the] vaccine.

But since we don't understand for an individual what an individual's protection is going to be, because of the wide variety of cancer therapies that patients receive, what my general approach is to say, even if you've been vaccinated, to continue to be cautious. And I think that's particularly important with the Delta strain, which is much more infectious and much more able to spread amongst individuals that our patients with cancer, despite receiving full doses of vaccine, should continue to mask up in public, should try to avoid close contacts with large groups, to socially distance when possible, and to have discussions with everyone in their household to get vaccinated.

I even recommend to try to avoid interacting with other households where there are others that are not vaccinated because of the advantages that you get from having those around you vaccinated. This is really challenging, as you can imagine, within the patients who live in households with young children who are going back to school.

And so in those situations, having a discussion with the school if possible and having your children wear masks when they go to school can be helpful. We don't know the total benefit in terms of protecting an individual at home, but any way that you can protect yourself from getting COVID-19 is really critical.

So what I suggest is [to] get everyone who can be vaccinated vaccinated, wear masks in public, socially distance, wash your hands really well, and avoid crowds as much as possible. And if it means doing a few more Zoom calls with your family that have unvaccinated individuals, then that's something that may need to be something you do.

And let's say you're an older patient who's a patient with cancer who's received your third dose of the vaccine, and you want to go visit your grandchildren who are unvaccinated. Well, have a conversation with family about that. First, is it necessary to do in-person?

If you can do it by virtual methods, you can. But if you do need to go see them, plan to do those interactions outside and consider wearing a more protective mask, something like a KN95 or a surgical mask with potentially even a cloth mask on top--so a double mask. But I think a can KN95 mask would be my best recommendation.

And then you can interact with them outside and not indoors where the potential risk of transmission may be higher. And that may not be what everyone wants to do, but it's all about being there for your grandchildren and your family for the long term, and that's the goal in all of this is to protect our patients as long as we can.

Dr. John Sweetenham: Great, thanks, Steve. That's great common sense advice, and I think a great way to round out our conversation today. I want to thank you very much for sharing the update on COVID-19 third shots today for our patients with cancer. And also once again, just to say thanks for the work that you've been doing with the NCCN and beyond in helping the oncology community navigate the pandemic. So, [I] really appreciate your time today.

Dr. Steve Pergam: Well, thanks for having me, and best of luck to all my colleagues out there and to all of the patients who are listening in. Know that all of us are working really hard to do what we can to protect you.

Dr. John Sweetenham: Thanks, Steve. And thanks to our listeners for joining us today. If you enjoyed this episode, please take a moment to rate and review us wherever you get your podcasts. Thanks and goodbye.



Dr. John Sweetenham: None disclosed

Dr. Steve Pergam:

Research Funding: Global Life Technologies, Chimerix, Merck & Co., Sanofi Pasteur

Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.