The Expanding Role of CAR T Cells in Lymphoma and Leukemia - Episode 9

R/R NHL: Candidate Identification and Referrals

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Stephen J. Schuster, MD: The next part of the discussion is based on our experiences and what is being captured in the literature. These are points that are practical for those physicians who are in practice and treating patients with lymphoma but are not at a center that is necessarily doing CAR [chimeric antigen receptor] T-cell therapy. And that relates to identifying who’s the right person for CAR T; well obviously, we can only go by the label at these prices. But timing is a more important issue. Identifying and timing are related because you can identify when you’re too late. Let’s talk about timing and identification of the patients you would refer to CAR T-cell therapy.

David Miklos, MD: You started with the obvious one. You can be too late, to not get the referral going early when a patient is showing a refractory response to induction chemotherapy. Even though you must give that second round of salvage by label, you know that’s not likely to work, and you better be calling your referral center. And secondly, the patient who has no evidence of response after 1 round of salvage, it’s not going to get better after the second. You’re still going to give that therapy, but please call. Because low disease burden, good performance status, low LDH [lactate dehydrogenase], and low inflammatory state are 4 of the 5 now repeatedly identified poor prognostic signs. They’re all related to waiting too long.

Stephen J. Schuster, MD: Yes, and that extra cycle of chemotherapy further depletes the lymphocytes in patients for whom you may need to manufacture cells. You’re not doing a patient a favor by waiting.

Matthew J. Frigault, MD: Not only that, but some of the newer therapies that are coming out that are competing with the same indication have impacts in terms of the types of quality of cells you’re getting, your likelihood of manufacturing these cells. And so dragging your feet and being pulled to give a therapy that may contain something like bendamustine will impact your ability to collect, manufacture, and get a patient to infusion quickly.

Loretta J. Nastoupil, MD: Matt, you touched on this earlier. One of the biggest issues we have is we know identifying patients early and introducing this is great. But we partner with community oncologists oftentimes. And these patients get to us, and they’re in a state that we’re nervous about toxicity and efficacy. How do you optimize these patients? We now have things like bendamustine, polatuzumab, rituximab, though I agree, I have significant concern about giving them bendamustine before collecting those cells. We may have something like tafasitamab, which is a naked CD19 antibody, in combination with lenalidomide. There is a huge unmet need for how we bridge these patients, because we know those who need bridging are going to do worse, based on the fact they need to be optimized. That’s where I struggle. What are your thoughts?

Stephen J. Schuster, MD: One thing that’s very important is the bendamustine/polatuzumab issue, because the data had been presented. There’s a nice response rate in people that are refractory to the common salvage regimens. And bendamustine is a wonderful lymphodepleting agent. We use it at Penn [Abramson Cancer Center] more often than CyFlow [flow cytometer]. Results are not worse than other people’s, and I have lymphocyte data to substantiate what it does to the lymphocyte count. It makes no sense to be giving that and then sending them to a place where you’re expecting them to pherese and make CAR T cells. That’s clearly, before you give bendamustine to somebody….

Matthew J. Frigault, MD: Most people on this talk and most people doing CAR T-cell therapy are happy to get a phone call or an email or any kind of communication to give freebie advice on how to strategize. Because one thing we can touch on here is that there’s a strategy of getting, at least in the autologous T-cell setting, a strategy of getting a patient to an infusion safely while still simultaneously optimizing them for success.

David Miklos, MD: Recognizing you still have other hurdles to get over—scheduling, insurance authorization. The 5 of us probably take referrals for the next day, because we know that the timeline is short for that patient, and the success is dependent on getting it going fast.

Stephen J. Schuster, MD: And now with telemedicine, you can even see the patients without going to the office. There’s no excuse not to see them the next day. You can even see them at night before you go to bed, David. Yes, there is no excuse to not send the patients. We can see them right away.

Transcript Edited for Clarity