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Breakthrough COVID-19 Infection in 10% of Patients With Blood Cancer, LLS Data Show

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About 10% of patients with blood cancer, especially those with B-cell lymphomas, who did not make anti-spike antibodies after vaccination experienced breakthrough COVID-19 infection, said Lee Greenberger, PhD, chief scientific officer, Leukemia and Lymphoma Society.

Data presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition from the Leukemia and Lymphoma Society (LLS) National Patient Registry show a moderate link between the time that elapsed between a patient’s third COVID-19 vaccination and a breakthrough infection. Lee Greenberger, PhD, chief scientific officer, LLS, explains how COVID-19 data from the registry help inform clinicians and committees that develop guidelines about vaccination recommendations for patients with leukemia and lymphoma.

Transcript

How can data from the registry help inform COVID-19 vaccination recommendations for patients with leukemia and lymphoma?

What we've learned from the LLS registry, as we've analyzed the response to the COVID vaccines and then the breakthrough infections that happened after the vaccinations, is we've learned there are 2 studies that we've done. One study has been completed that's being reported here [at ASH 2022]. That was work done during the Omicron surge, which we saw a big surge in COVID infections about last year, coincided with what we saw in the public domain as well. We saw about 10% of the blood cancer patients reporting they got breakthrough infections, and the infections tended to occur in people with B cell lymphomas. That is what we expected, because the patients who don't make anti-spike antibodies in response to the vaccines would appear most vulnerable.

Now, the surprising thing that we found was actually the breakthrough infections were occurring in people who didn't make anti-spike antibodies, and then there were patients who did have good anti-spike levels, about what you might expect for normal patients, they were getting breakthrough infections as well. Why was that? The reason why we think it is, is because the virus was changing, as it has been up until really just present day. So what's happening is, the vaccines are working, the vaccines are becoming outdated, they're not working as well against the new strains. So people in January, when the Omicron surge was happening, still had the old vaccination. So what you see is, pretty much you could make an anti-spike response to the vaccine or not, you're still getting breakthroughs, and the breakthrough was still about 10% across the board.

What we did see however was, in the patients that got hospitalized—we had 90 patients who got hospitalized—10 of those patients, we had anti-spike levels. And 7 out of the 10 patients that did not make any anti-spike response at all and wound up in the hospital, and the 3 additional patients had low anti-spike levels. We don't know what the level of anti-spike level should be to provide protection. I think that's a fair statement. However, we know that when it's low, those are the patients who are vulnerable. So what I'm saying is, 10 out of 10 patients, either did not make anti-spike detectable levels or had very low levels, and they wound up in the hospital. That's a clear warning sign that patients who are not having a good response to the vaccine are the ones that are most vulnerable. And those patients need to be take precautions: social distance, get everybody in the family vaccinated, continue to wear masks, avoid crowds, those type of things. And I have to tell you, speaking to multiple patients, it's a big concern. And there are hundreds, thousands of patients who have, for example, CLL, one of our largest populations of B cell lymphomas, who are at risk either because of the disease, because of the disease treatment, and because of the vaccines not working at that time.

So now roll it ahead. We did a second study, which we have not shared the data with, but this study was completed in August. We look between April and July of 2022 and asked who got breakthrough infections again. The reason why we did that was because we knew that we would be getting the post-Omicron variants that were beginning to take over. What we saw was a breakthrough rate of about 15% of patients. We also had about 1200 patients that got Evusheld, the monoclonal antibody combination which is FDA emergency authorized to protect against infections. We saw breakthrough infections in patients who got Evusheld as well. What that was telling us was that the virus was changing. There were laboratory studies that had used Evusheld in laboratory studies saying the Evusheld combination antibody is not working as well, it's beginning to lose efficacy. It clearly was not as efficacious as the data that supported the emergency authorization, which was really against the Wuhan strain.

Now roll it ahead. The virus is changing. It's become more resistant to the monoclonal antibodies and to the original vaccines as well. So what you're seeing is you're seeing breakthrough infections on patients that got Evusheld. By the time that data was assembled, which we knew back in August, they said, "Hey, wait a minute, there's a problem here with Evusheld." Now roll it ahead till December, to today, and the virus has changed again. What you're seeing is that the virus is mutating, it's developing resistance to the original vaccines, to bebtelovimab, to Evusheld, to the point where bebtelovimab, the FDA basically said you can't use it anymore. We even know that for Evusheld, based on the laboratory studies saying Evusheld will not have any efficacy, we don't have the clinical correlate of that, but based on our studies with the initial breakthrough infection and now with the laboratory data saying Evusheld has even reduced efficacy to the new strains, we think that the original will have very little utility, unfortunately.

What does this mean? So one is, people need to get the latest vaccine. That does impart some protection, not as complete as protection as it did where he had the Wuhan strain, but there is some protection. People need to get that vaccine. Every blood cancer patient should get that vaccine. It might help, it's highly safe, and it might be effective. Outside of that, if a blood cancer patient develops an infection, whether you have a B cell malignancy where we worry about not making good antibodies—which, by the way, will happen even to the new vaccine, that's what we expect, we haven't actually looked at it but we fully expect that—because the B cells are depleted. They're not either not working well or they're just not there because of the therapies. We expect that to happen. In the event those patients do get an infection, within 5 days they really need to get in touch with their clinicians, their treating physicians. Because paxlovid, the antivirals, will still work, it's highly important that those patients actually get paxlovid to see if we can limit the time that they get the infection.

Now, that all said, the most serious situation is patients that have long-term infections, and I'm not talking about the long-term COVID. That's a different thing. I'm talking about patients who have persistent infections, and we've seen that in some of the patients. Those are the patients that we're really concerned about because it's been 5 days, paxlovid is probably not going to work very well, the virus is still there, it can be detected either on PCR or rapid tests. And we know from studies that have been done actually years ago that the virus will mutate in those patients and those become the resistant strains. If those get out into the public domain, it's not only a problem for the patient. It's now a possibility that the whole population could take that viral strain up, which will be resistant. There are implications way beyond just a patient that has long-term COVID. There's something called long-term COVID. In other words, the infection is cleared but the symptoms still remain. That's a different story. We don't know about blood cancer patients, whether they're going to be any different than normal, healthy individuals, but we certainly have seen patients tell us they have long-term symptoms that still linger.

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