Third Dose of COVID-19 Vaccine May Increase Protection in Immunocompromised Patients

The Food and Drug Administration (FDA) recently authorized a third dose of either mRNA COVID-19 vaccine —Pfizer or Moderna — for patients who are immunocompromised, including certain patients with cancer, as they may not have a strong of an immune response as others in the general population.

“This country has entered yet another wave of the COVID-19 pandemic, and the FDA is especially cognizant that immunocompromised people are particularly at risk for severe disease,” said Acting FDA Commissioner Dr. Janet Woodcock in a news release. “(This) action allows doctors to boost immunity in certain immunocompromised individuals who need extra protection from COVID-19.’

CURE® spoke with Dr. David E. Cohn, chief medical officer at The James Cancer Hospital and director of gynecologic cancer research at The Ohio State University Comprehensive Cancer Center in Columbus, to learn more about the important getting a third vaccine in patients who are immunocompromised, how it may affect their treatment course and how this FDA authorization does not mean that either mRNA vaccine is ineffective.

Why is it important for patients who are immunocompromised to get the third vaccination shot?

The reason why it's important for the immunocompromised population in general to have a third shot is exactly the reason why it's called the third shot, is that they may have never had the level of immunity to keep them from getting severely ill or dying from (COVID-19). We know that in a certain group of immunocompromised patients, when (researchers have) evaluated them, they're at higher risk for getting (COVID-19) at baseline, they're at higher risk for getting severe complications related to (COVID-19) as well. And if you don't have the ability to get your immune system up above that threshold, then you're especially vulnerable to getting (COVID-19) and getting sick from (COVID-19) as well.

What patients do you think would be best suited for this third dose? Is it does it differ by cancer or treatment method?

It's probably the hardest question that we've had to answer, and there's not a black-and-white answer to it. If you took a look at all different types of patients, there's different patients that have different levels of potential immunity to COVID-19 after vaccination. There's different cancer treatments that lead someone to be more or less immunocompromised, and there's actually cancers in and of themselves, which leaves somebody to be immunocompromised even without having treatment.

The way that I think about it is, the longer that someone is from completing therapy for cancer, the better their immunity is going to be, the ability to mount an immune response will be. The further they are from getting chemotherapy or radiation, the more out they are now to full immune response as well. It's related to the time from diagnosis, it's related to the time from treatment.

Then there's specific diseases which are, by definition, ones which cause immunocompromise. Those are certain types of chronic leukemias, regardless of when you're diagnosed or what your treatment has been.

Most institutions are choosing some combination of time from diagnosis, certain types of treatments and certain types of cancer to identify that population. The way that I would think about it is that if you make the population too restrictive, if you narrow the group that you're going to call immunocompromised, then the biggest risk is that you're going to end up missing somebody deeming them to be appropriately protected against (COVID-19), when they actually still have a substantial risk and therefore need that third vaccine. And if you're overly broad in your criteria, then you're going to end up vaccinating many individuals that technically don't need to be revaccinated or have an additional dose. That gets into an issue of over allocating your supply of (COVID-19) vaccination to a population (where it) really wouldn't be beneficial.

What is the different between a booster shot and a third dose?

It's more of this semantic nomenclature issue between booster and what I think we and the FDA have deemed a third vaccination or an additional vaccination. It’s really important, because the purpose in this immunocompromised population is to get their immunity levels up to a certain level that allows them to be protected against severe complications like hospitalization or death from (COVID-19).

In this population, the theory is that they've never actually had enough immunity to be fully protected, like the general non-immunocompromised population. That's a third dose to hopefully get them above that threshold, whereas the general population has talked about a booster shot, where in theory, they've had adequate immunity to get them above that threshold, and then over time, that immunity has decreased or waned to the point where they need kind of an additional booster to get them over that threshold that they used to have already.

Are there any plans for additional doses of the Johnson & Johnson/Janssen vaccine?

At this point in time, the FDA has not released similar guidance for the Johnson & Johnson/Janssen vaccine for a second dose in that population, but it certainly is an area of continued interest. And I think it's anticipation that something in the future may come out that would describe a strategy for those individuals who are immunocompromised, who have had the Johnson & Johnson vaccination.

Do you think this is something that patients who are immunocompromised will have to undergo every few months, or will they have to be tested and studied in a way to see whether their immune response builds up to the level it needs to be with this third dose?

Interestingly, the FDA had actually (issued an) explicit statement that blood testing for antibody levels or immune response is not recommended at this point in time to demonstrate response to vaccination. I don't think that that's going to be a strategy that we see in the future.

I think that the hope is that we'll be in a position of protecting a larger population than we have with two doses by adding the additional third dose. Whether or not there’s going to be more doses in the future, if (the third dose) is adequate, I think is it is a crystal ball question and something to keep an eye on as research continues.

I know that in our institution, we started doing our third-dose vaccinations earlier this week. We have an ongoing study in our cancer population, which does just that: we do blood testing, and we do (COVID-19) testing on a regular basis following vaccination to see actually what is the response from a research perspective, see if that'll help inform the decisions about future strategies for vaccination.

How are patients at your institution responding to this third dose? Are they receptive to it?

I was there yesterday, watching the vaccine center operations. It's a population that's really motivated to do everything that they can to protect themselves. These are groups of patients that are worried about their own personal health, but also patients that have done an incredible job in doing the right thing from a public health perspective of hand washing, distancing, masking and controlling their environment. I think that they want nothing more than just to get back towards normal to be with their families without the fear of themselves or others being ill.

What we found is that with the first two vaccinations, when we began rolling them out in the winter and spring to these populations, that was a really motivated group. They were in line as soon as the vaccinations became available. (We) have a very high uptake of vaccination in our institution for those immunocompromised patients. I think that they're equally excited now, recognizing that this could be their path, again, to full immunity and things giving back towards normal again.

Does the third dose cause similar side effects to the other two doses? And would this affect a patient’s course of treatment?

It would be expected that the side effects would be very similar to the first two doses. We know that, anecdotally, the second dose seemed to have worse side effects than the first when they were three or four weeks apart, depending upon the manufacturer. Most of our patients now are more than that period of time away, so we don't know what's going to happen with the side effects with a third dose, I but don't anticipate that it's going to be any worse than what they had with either of their previous two doses.

The same strategy that we had with the other two vaccinations is that at certain times, I wouldn't say we've thrown off the timing of treatment, but the timing of the vaccine should be discussed with your health care provider if you're a patient who's immunocompromised thinking about a third vaccination. Some chemotherapy regimens, you wouldn't want overlapping side effects of the vaccine plus chemo. Certain chemotherapy regimens or other treatment regimens, you might want to time it around someone's risk for their white blood cell count being low or their platelet count being low. It's important to have that conversation with their health care providers to make sure that the timing is optimized for both vaccination and treatment.

What advice would you give patients and their caregivers?

I think that the most important other piece of information to me is the logical information that the vaccinations that we're talking about now of using a third one, the strategy that we're employing now is not because of the fact that the vaccines don't work, meaning the vaccines are very effective at preventing severe illness or death from COVID-19 in the general population. The reason that this strategy is started is because these effective vaccinations may not be as effective in very specific circumstances. It's not a failure of the vaccine, as much as it's a failure, if you have to say that, of the person who's receiving the vaccination of mounting that adequate immune response. It's really important for the general population to recognize that if they have not yet been vaccinated, this is the most important thing that they can do to protect themselves and to protect their communities against severe illness from COVID-19.

I think that the second point that's really important is that for those folks that are immunocompromised and are thinking about a third vaccination, it’s critically important that their close contacts become vaccinated if they're not vaccinated at this point in time, because those unvaccinated closed contacts could put an immunocompromised patient at very high risk for getting (COVID-19) and then those complications as well.

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