What is hypogammaglobulinemia?

What is hypogammaglobulinemia? Is it common in a CAR T cell recipient? How long does it last? How is it treated? Hypogammaglobulinemia or hypogamm, as you may hear it, or low IgG is a very common side effect from BCMA-directed CAR T therapy. And the reason for that is that the globulins, the IgG, is produced by plasma cells. So if you have an effective therapy that kills plasma cells, it doesn't know what a good plasma cell is or a bad one. It just kills all of them. So in fact, it's actually a bad outcome or a side effect of a very good outcome, clinical outcome. And so sometimes when we see that, we know that our therapies worked well, but maybe a little too well. And so you can see oftentimes in your labs that the IgG level will be low. And that's what the diagnosis of hypogammaglobulinemia is. And when that happens, we start to think, okay, maybe patients are more at risk for having infections. Remember, the whole point of plasma cells is to produce these IgG, IgA, et cetera, to help you to fight infections. So when these are low, you worry that you might be more immunocompromised. And it's true. Many of our patients, many of you, might have noticed that you get a few more colds than other people do. You're a little bit more susceptible. Now our patients do try to be very careful about things like masks in a crowded area or being sure to wash their hands, being sure to make sure you don't necessarily come into contact with people who you know are sick. But of course, you have to live life. And because of this, a lot of times when patients have low IgG or hypogamm, we might give them something called IVIG or intravenous immunoglobulin. And this is really a pooled sort of source of immunoglobulins from a bunch of people, healthy donors, to help us to give to patients to replenish what they're missing because we've had such effective therapy. If you look at all the CAR T cell studies, you'll see that a lot of patients in these studies had low IgG. And what we started doing when we started these trials was just arbitrarily at a cutoff of 400, starting to give supplemental IVIG or intravenous immunoglobulin, really because we didn't want patients to have any more side effects than they would already have from certain therapies and from the CAR T therapies. What I would say is if you're a patient who has a low IgG level, it's important to talk about this with your physician. It doesn't necessarily need to be treated. What we usually say is that this can be treated if you have a lot of infections. I'm a little bit more likely to treat it if people have gotten BCMA-directed therapy because that therapy is so effective and it's so long-lasting oftentimes that we don't want to have patients with this low IgG level for so long. And that's why a lot of times we will give supplemental IgG for patients who've gotten CAR T therapy. The length of time that the low immunoglobulin G lasts varies between patient to patient. And sometimes when you see the IgG rising, it might not be the good IgG. So this can be ups and downs for patients looking at their labs. I would say it's really important to just check every lab result and discuss it with your physician because it can go in either direction. And you want to make sure you also tell all your symptoms because if you're having more infections, you may require supplementation.