ASH 2022: COVID-19

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

About 10% of patients with blood cancer experienced breakthrough COVID-19 infection, said Lee Greenberger, PhD, chief scientific officer, Leukemia & Lymphoma Society (LLS). This was true among those with B-cell lymphomas who did not make anti-spike antibodies after vaccination as well as some who did make anti-spike antibodies, according to data from the LLS National Patient Registry, which was presented during the 64th American Society of Hematology (ASH) Annual Meeting and Exposition. Registry data show a moderate link between the time that elapsed between a patient’s third COVID-19 vaccination and a breakthrough infection, Greenberger told Evidence-Based Oncology™ (EBO). This interview is edited for length and clarity.

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

Greenberger: We’ve learned from the LLS registry as we’ve analyzed the response to the COVID-19 vaccines and then the breakthrough infections that happened after the vaccinations [from] 2 studies that we’ve done. One study has been completed that’s being reported [at ASH 2022]. That was work done during the Omicron surge, which we saw a big surge in COVID infections last year, which 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 was 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 typical patients—they were getting breakthrough infections as well. Why was that? The reason why we think is because the virus was changing, as it has been up until present day. So, what’s happening is the vaccines are working, [but] the vaccines are becoming outdated; they’re not working as well against the new strains. So, people in January 2022, when the Omicron surge was happening, still had the old vaccination. 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 who got hospitalized—we had 90 patients who got hospitalized—for 10 of those patients, we had anti-spike levels. And 7 out of the 10 patients who 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 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 take precautions: social distance, get everybody in the family vaccinated, continue to wear masks, avoid crowds....Speaking to multiple patients, it’s a big concern. There are hundreds, thousands of patients who have, for example, [chronic lymphocytic leukemia], 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....

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 breakthrough infections in patients who got Evusheld. By the time that data were assembled, which we knew back in August, they said, Hey, wait a minute, there’s a problem here with Evusheld. Now roll it ahead to 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 for bebtelovimab, the FDA basically said, “You can’t use it anymore....”

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 we 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....In the event those patients [with leukemia or lymphoma] 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-19. 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 [polymerase chain reaction] or rapid tests. And we know from studies done 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-19.

Reference
Reddy ST, Saltzman LA, DeGennaro LJ, et al. Breakthrough COVID-19 infections in patients with hematologic malignancies during the Omicron (B.1.1.529) surge: data from the patient-reported Leukemia & Lymphoma Society National Registry. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA: Abstract 2300. https://ash.confex.com/ash/2022/webprogram/Paper167321.html