Andrew Schorr (00:05): Hello and welcome once again to Patient Power. I'm Andrew Schorr in San Diego. We're connecting with a leading lymphoma expert and that's Dr. Joshua Brody who's at Mount Sinai Medical Center in New York City. Welcome back to Patient Power, Dr. Brody.
Dr. Joshua Brody (00:22): Andrew, thank you so much for having me back. Good to see you.
Andrew Schorr (00:25): What is your title there? Because I know you specialize in the treatment of lymphoma and the research.
Dr. Joshua Brody (00:32): I think what I'm writing on the bottom of my emails is director of the lymphoma immunotherapy program because that is the focus of our research both in the lab and in our early phase clinical trials. But to be clear, lymphoma, we actually include CLL amongst those. Patients with all types of lymphomas and CLL are those that we focus on in the clinic.
Andrew Schorr (00:52): Okay. Well, for this segment, we're going to talk about non-Hodgkin lymphomas of which there are many. And a lot has been happening. And you've been part of the research. Let's start this way, Dr. Brody, where are we now with the therapies that are available approved and where are we headed?
Dr. Joshua Brody (01:14): Andrew, it's a great question, because we have always been a bit lucky in lymphomas, especially in B-cell non-Hodgkin's lymphomas, to have already some better success in treating our patients and better progress over the past 20 years. But over the past few years, we've got just luckier on top of luckier. We don't want to oversell it, because there's still a lot of patients that don't do as well as we would like. But although, we were already giving better outcomes to many patients with the different types of non-Hodgkin's lymphomas, the progress in the last few years, so I'll just examples of a couple of now FDA approved therapies, but also the pipeline of what will get approved in the next couple of years is as exciting or even more so. But just over the last couple of years, easier access to different types of CAR T-cells and almost science fictiony sounding type of immunotherapy, where we take out some of a patient's immune cells with a type of a blood draw.
(02:10): We actually do gene therapy on those T-cells to make them into anti-cancer, anti-lymphoma T-cells and then reinfuse those CAR T-cells. They were T-cells when we took them out, we put in this gene called the CAR and now we call them CAR T-cell. Reinfuse those CAR T-cells into patients and they have amongst the most impressive potency of any therapy ever for lymphomas. Maybe one of the catches is that they're not completely benign. There's an important side effect that I'll mention. But in the past couple of years, more FDA approvals for different types of CAR T-cells, CAR T-cell for different types of lymphomas, diffuse large B-cell lymphoma, mantle cell lymphoma, and now follicular lymphomas and even for earlier lines of therapy.
(02:55): And perhaps, one of the biggest results was a couple of randomized trials. Big trials proving that for diffuse large B-cell lymphoma, one of the most aggressive types of (NHL) non-Hodgkin's lymphoma that to give those CAR T-cells as a second-line therapy as opposed to third-line therapy, we've been using as before was even more effective and probably safer than the prior standard of care, which is autologous stem cell transplant or we sometimes say (BMT) bone marrow transplant. CAR T-cells now as standard second-line therapy for many patients with second-line relapsed or refractory diffuse large B-cell lymphoma.
Andrew Schorr (03:31): Okay. Now, you alluded to a side effect and I think you're talking about cytokine release syndrome. What is that? And have you all been learning how to control it so that CAR T is more tolerable?
Dr. Joshua Brody (03:44): Yeah. Cytokine release syndrome, one of the most common and significant and then one other probably maybe even a bit more important now, we call it ICANS, I-C-A-N-S. It just means neurotoxicity, which results similarly from the CAR T-cells. This cytokine release syndrome is an infection without a bacteria or a virus. It's just your immune system gets over inflamed. And patients can end up with high fevers and in the intensive care unit with low blood pressure. And then, the neurotoxicity, the ICANS syndrome is similar instead of happening on day three, four, like the cytokines syndrome, it happens on a little bit later day six, seven, eight, somewhere around there. And mostly manifest as confusion even sometimes hallucinations. I had a patient who stood up and started peeing on the wall and when we said, "What are you doing?"
(04:38): He said, "No, no, that's what you do." Just confusion. But even a much worse versions of that. People sometimes would get seizures, sometimes become encephalopathic, just unresponsive. And for both cytokine release syndrome and this ICANS neurotoxicity syndrome, we've made a bit of progress. I'll tell you the most progress we've made has not been very fancy, medical or science new therapies, it has been just a better understanding. The worst predictor for cytokine release syndrome is that patients that are going into CAR T therapy with high tumor bulk have the worst manifestations of that.
(05:12): Now, it's a more common practice to try to debulk the tumors to use some bridging chemotherapy or any kind of other therapy to get patients to go to CAR T-cell therapy with smaller amount of lymphoma going in. And that has been beneficial in decreasing amounts of cytokine release syndrome. Some of their standard therapies, one is called tocilizumab, others are just high doses of steroids, can be pretty effective in treating this (CRS) cytokine release syndrome. And because of that, we have many fewer high-grade CRS problems. That neurotoxicity still a problem, still 10% to 20% of patients getting a bad version of that after CAR T-cell therapy. A great and effective therapy still in working on improving these side effects.
Andrew Schorr (05:57): All right. One other area, I wanted to ask you about. This whole term of immunotherapy. In the solid tumor world, there have been these checkpoint inhibitors that have been used in combination with other drugs to help people even with lung cancer surviving. Did those kind of drugs play a role at all in lymphomas?
Dr. Joshua Brody (06:22): The successes have mostly been for these solid tumors, lung cancer, some of these others. In lymphomas, they've had profound benefit in one type of lymphoma really, which is Hodgkin's lymphoma. Hodgkin's lymphoma, Andrew, you know very well, are more commonly amongst younger patients, 20 and 30 year olds. And we were doing pretty well with them already, curing a good majority of them with standard chemotherapies and also with antibody drug conjugates now, one called brentuximab vedotin. But these anti-PD-1 antibodies hugely effective for Hodgkin's lymphoma, we routinely use them as a second or third-line therapy. We may start using them as a frontline therapy for Hodgkin's lymphoma. For non-Hodgkin's lymphomas, they mostly have been not effective. There's a couple of exceptions there, but mostly not helpful. We are trying to figure out if there're ways that we can make them work better for non-Hodgkin's lymphomas. But yeah, their success has been mostly in Hodgkin's lymphomas so far.
Andrew Schorr (07:16): If you pull it all together, Dr. Brody, for our audience generally it seems you feel your field is making a lot of progress. You and your colleagues, thank you very much. And people should feel generally encouraged, but they need that dialogue with a knowledgeable doctor about their personal situation. What could apply either approved medicines or what's being investigated?
Dr. Joshua Brody (07:45): Absolutely. I mean, there are great doctors in academia, great doctors in the community practices. Tough for a patient to know, there's no great believably Yelp for doctors. How do you know if your doctor is great? And the simplest metric should be, "I ask my doctor questions, does he give me what seems like reasonable answers that I can understand?" Doctors should all be able to still speak the common language of English. Even if we speak medical or science sometimes, we should be able to speak English and we should be able to answer your questions in a way that makes sense to you.
(08:16): And if you don't feel that that is thoroughly and thoughtfully accomplished, no doctor should ever be upset about you getting a second opinion. I have my patients get second opinions at other places. This is the patient's wellbeing, so that is easily a priority over some doctors' ego. I think that always getting, especially in some of these rare disease that you mentioned, where someone that sees this one disease all day instead of seeing many different types of cancer would be worthwhile for all these folks to get second opinions at least until they get the comfort that their doctor is assessing them as an individual, for sure.
Andrew Schorr (08:53): What great advice. Thank you, Dr. Joshua Brody from Mount Sinai for giving us this overview of progress in NHLs. A little bit about Hodgkin's and the mention also us understanding about the more rare ones, including T-cell. We wish you God speed with your work, right? And all the hieroglyphics you've got back there on your whiteboard. And thank you for being with us once again on Patient Power.
Dr. Joshua Brody (09:23): Andrew, good to see you. Thank you so much.
Andrew Schorr (09:25): I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.
