VIDEO: Expert discusses strategies to combat infections in patients with CLL

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With CLL, we know there is a component of T cell dysfunction, which is kind of under considered, I think, you know, it's not as well known, it's harder to quantify, but we know that there are secondary malignancies with CLL skin cancers are very prevalent. I always advise folks to where at least SPF 30 or greater and just be mindful and diligent about any skin lesions, for example, and do routine health screening. Just from CLL itself, there's a T cell dysfunction, which is actually one of the mechanisms or pathogenesis of disease progression, right?

Where these CLL cells secrete these immunosuppressive cytokines actually, and they directly modulate the T cell microenvironment, and it's one of the ways that they can actually progress. So, the higher the bulk of disease, the greater the degree of T-cell dysfunction, and with that comes atypical infections. And so oftentimes, viral infections, certainly COVID was clearly devastating, especially in the setting of anti-CD20 based treatments and B cell depleting therapies. In my practice, I do screen for quantitative immunoglobulins in the beginning and as well as actually for monoclonal proteins.

And if patients have an IVIG, IgG level rather of less than 400, I will offer IVIG, you know, 0.4 grams per kilogram every 28 days and titrate to a trough IgG level of 400. If there are known infections, recurrent URIs, even UTIs, other kinds of infections that you see, definitely wanna consider hypogammaglobulinemia in treatment, particularly those folks who have, you know, CLL that's advanced, that's in the early treatment period, right? Especially, you know, with the anti-CD20 based therapies, in my opinion, BTK inhibitors can also be immunosuppressive. I will basically also consider acyclovir. I'm very pro-vaccine.

I do respect patients' wishes. I know there's a lot of conflicting information out there about vaccinations, but I am personally pro-vaccine as long as they're non-live viral. So, Shingrix, for example, is one of those vaccines that's not a live virus that I would encourage RSV COVID, frankly, you know, I do recommend vaccination, influenza, of course, when it's due in the fall. We also know from our data here at Roswell Park and our investigation that folks with CLL don't respond very well to vaccines or frankly from prior infections. So, because of the B cell dysfunction, which is represented most clearly by acquired hypogammaglobulinemia and then further exacerbated by early treatment and then the T cell dysfunction, there is a poorer than most response to vaccination, which can be pretty significant.

So, about 50% of folks who are treatment naive with advanced CLL will respond and create titers to vaccines. On treatment, it's more like 25% for some folks. And sometimes I will actually adapt treatment or even hold treatment if there are active infections. So, for example, someone on a BTK inhibitor, you know, well controlled on that without any concern for progression or anything like that, I'll often hold the BTK inhibitor temporarily while they get over their acute illness and then put them right back on it without any issues. So, about a week delay for me is safe and I kind of go from there.

But just know that people are with CLL especially on treatment are immunocompromised or at least immunosuppressed and will benefit from more attention to detail and prevention for infection, including vaccination. I will lastly say that we're waiting with some bated breath for some of these new injectable monoclonal antibodies that are preventative. So, Evusheld was previously approved in this space to prevent COVID specifically, but with viral mutations they became ineffective and it was pulled from the market. There are some EUAs, one active and with very early data.

So, we're considering, you know, some of these newer agents for that, not quite ready for prime time. And then there's kind of an Evusheld 2.0 if you will, that's also being developed, so we will stay posted for those. But I'll end up offering those treatments, especially for the most immune suppressed patients we have. CLL post CAR T would be by far the worst, right? Highest risk, for example, and you look for atypical infections and oftentimes if there is an infection that's recurrent, I will refer to infectious disease as well to help me augment prophylaxis and look for weird infections.