MPN Workshop of the Carolinas 2025 | Strategies for mitigating infection risk in patients treated with CAR T-cell therapy

So that’s a field that is gaining a lot of traction now that we’re managing CRS and ICANS, I think with a fair amount of success post-CAR-T, but infections is what’s surprising to us in that it’s a pretty high burden of morbidity and mortality post-CAR-T. We and others have published sort of the rates of infections, the factors amounting to the risks, including hematopoietic toxicity and immunosuppression and so forth. And the rates are high, and it is probably one of the highest causes of non-relapsed mortality post-transplant. So certainly an impactful area to focus on. 

You’re asking about how we can mitigate infections. and we published on this a little bit in as a part of the ASCT guidelines and certainly there’s other material out there to look at, but we’re recommending antimicrobial prophylaxis so bacterial and fungal for the duration of neutropenia; acyclovir or valaciclovir for shingles prevention for six months to a year; PJP prevention for six months to a year, and you can use CD4 recovery to figure out how long you want to use the PJP prophylaxis, but that’s prevention. 

Monitoring, the new thing that we learned with BCMA was CMV reactivation, and we saw that in a much higher proportion of people who had received a longer duration of steroids, and those are the ones where CMV monitoring needs to be done and we’ve been doing that. CMV disease is not very well reported but CMV reactivation is certainly reported in about 20% to 30% people. So keep in mind that that is possible and to monitor that when people are neutropenic for a long time or have prolonged use of steroids. 

The other thing is immunoglobulin replacement right. So in the multiple myeloma world we know that there is immune paresis we know that there is hypogammaglobulinemia by virtue of the disease and then by virtue of the CAR-T, and we at our center and other places I think are doing similar things that people are using immunoglobulin replacement very frequently in these patients and some of the registry data may suggest that people who got immunoglobulin replacement were at a lower risk of developing infections than those who didn’t. So something to think about. 

And then the last is vaccines, which is a bit of a gray area, post-CAR-T, people are doing different things. We’ve been following our autologous guidelines and revaccinating, but an ideal approach would be to see if there is immune response to some of the prior vaccinations, and if they are there, then maybe they don’t need to be vaccinated, whereas some of the other ones may be warranted. Long answer, but it’s a real concern and certainly needs steps to manage and prevent.

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