Monitoring and Mitigating Emergent Toxicities During CAR T-Cell Therapy

Joshua Richter, MD, and Marco Davila, MD, PhD, spoke about the roles that academic treatment centers can play when mitigating toxicities associated with CAR T-cell therapy among patients with multiple myeloma. With clinicians learning about new toxicities “on the fly,” Richter noted that collaborations with colleagues who specialize in gastrointestinal (GI) oncology or infectious disease may help with resolving some atypical toxicities that may appear. Overall, Davila said that toxicity management for this patient population is improving, although clinicians have a responsibility to communicate advances in prophylactic strategies to referring partners.

Davila is physician–scientist and service chief of the Lymphoma–Myeloma Adoptive Cell Therapy Service at Roswell Park Comprehensive Cancer Center. Richter is associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and director of Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai.

Transcript:

Davila: I have another question, and since we're talking about the community–cell therapy relationship and shared care of patients: when you transition patients back to their community oncologists, how do you recommend that they manage these potential toxicities or screen for them? What role do academic treatment centers in general play in supporting the management of these adverse events?

Richter: This is a really important topic, and it's actually an evolution because I tell the local doctor [for] anything other than the sniffles, give me a call; we're learning on the fly about new toxicities. I remember when we first started doing this, the local doctor would say the patient's having diarrhea, and I would say, do a stool culture and give them loperamide [Imodium]. Now, with our better understanding of IEC colitis, I think our role is to say, "Oh, wait a minute, they're having that symptom. Let me get them to my academic GI counterpart," who is not just going to scope them, but send specific tests to differentiate: is this just an infection, run-of-the-mill [toxicity], or a CAR T–related toxicity?

Same thing from an infectious disease standpoint. Someone has an upper respiratory infection, and you want to give them azithromycin [Z-Pak]? Great. They're having fevers and you can't isolate why? Time to come back to the mothership for extended viral panel testing. Could this be CMV or EBV reactivation? Maybe [it’s about] getting our infectious disease colleagues, who have more experience dealing with some of the atypical infections that we see with cellular therapy.

Davila: Yeah, that's great to hear. It's been amazing to see in the last few years how rapidly we've been able to improve the recognition of some of these toxicities. Then, how do we diagnose them, how do we grade them, and how do we manage them? Sometimes, seeing them early, when this starts getting discussed, creates a little fear. It's like, “Oh man, this could be something bad.” But a lot of times, just being able to give it a name, and talking about it amongst ourselves—this worked, or this didn't work—being able to share these data with each other, we're able to then develop consensus criteria and management schemes. That was the case for the movement disorders and the long-term neurotoxicities. We all feel relatively comfortable that early identification and early intervention really does improve outcomes, and the same thing is going to be true for the IEC colitis.

To me, that's the big thing we worry about now, partly just because we recognize it. There have probably been patients where we missed this early on, and it was only until it happened again that we were like, "This is something real," and then you hear about it from other folks. I am really reassured that we're learning a lot. But the thing that happens to us is we have to make sure this stuff gets communicated to our oncology [and] referrer partners about how our practice is changing.

It may have been just a couple of years ago that we weren't monitoring for ALC, where we weren't intervening with prophylactic dexamethasone for ALCs, but now we are. If that happens in the community, now that we're discharging patients quicker to the community, that has to be something the community has to monitor as well. At least be able to offer them: what are we doing, and why are we recommending this? Overall, I'm very reassured that our toxicity management is improving, but it really is incumbent on us to make sure these advances are communicated to our referring partners.