What types of infections have been seen with Car-T and bispecific antibody therapy? Why are these infections prevalent? How are they managed?

So when we talk about infection risk after T-cell redirecting therapy, it really is a big concern and something that we, undertake a lot of interventions to try to prevent. So these infections can happen for a variety of reasons.

One, while these therapies are very effective at targeting myeloma cells, unfortunately BCmA target is also on normal plasma cells.

And so we're basically knocking out the normal plasma cells as well. And because a plasma cells job is to make antibodies, patients really don't make antibodies very well when on these therapies, you know, with the bispecific, because it's a more continuous dosing that persists for maybe a longer period of time, whereas with Car-T, it's definitely significant upfront and kind of wanes as time passes.

So that's part of the infection risk not making antibodies. Some patients have low blood counts during the course of these therapies. So usually more, you know, with Car-T it can be more severe and more prolonged.

So if patients have low white blood cell count and low neutrophil count, they are potentially at risk for more serious bacterial infections, fungal infections, things like that.

Not every patient has neutropenia or prolonged, but there is definitely a subset where that becomes a more significant concern.

With the bispecific antibodies, the neutropenia, or, you know, low blood counts tends to be more transient but still puts us at an increased risk for infection when that does occur.

As far as what types of infections we see.

So I kind of would preface it by saying anything can happen. Still, the common things are still the most common. So, you know, colds, upper respiratory tract infections, things that are more common but serious are pneumonias, which can be viral, which can be bacterial things like streptococcus pneumonia. you know, Covid 19 was seen on a lot of the clinical trials.

And obviously that was when the pandemic was at, you know, it's heights.

However, still things that, you know, viruses that we may get when we're not immunocompromised may be more severe. When you have received these therapies. despite common things being common, patients on these types of therapies are at risk for what we call opportunistic infections. So things that don't normally cause infection if you're not immunocompromised but can.

And so the one we most commonly think of is called pneumocystis or pjp pneumonia. It's a fungus that we all basically breathe in. But normally when our immune system is working, we we don't become infected. But after these therapies, the risk of that infection is very real. and so that's something to always consider.

Other infections that certainly can happen again.

You know, gastrointestinal infections, skin and soft tissue infections, urinary tract infection. So really any new symptoms, yeah, need to be brought to attention. And infection needs to be considered as a possible cause when on these therapies.

We do a lot of things to try to prevent this now, especially now that we know more about it. So, you know, previously we often gave IVIg based on what the IgG level in the blood was.

I think that's becoming less common. I think we know let's just give it regardless because we know the infection risk is high. So for our patients here who are receiving Car-T or bispecific antibody therapy, we give IVIg monthly at the start, to, you know, replace those antibodies that they're not able to make themselves. It's also important to continue to take, pills that try to help prevent viral and bacterial infection.

And fungal infection. So, we continue on either acyclovir or valacyclovir to prevent, shingles reactivation during this period of immunosuppression.

This risk of Pneumocystis or pjp pneumonia, we have multiple different therapies that we can use to reduce the risk of infection.

Most commonly that's a pill, called Trimethoprim / Sulfamethoxazole or bactrim.

But if patients are having low blood counts, we can use a different type of antibiotic, besides bactrim to accomplish the same things about reducing that risk. And then lastly, for patients who do have neutropenia or, you know, a more prolonged reduction in the white blood cell count, that may warrant going on an additional antibiotic or antifungal medicine to cover during that period of low white blood cell count.