Play PodcastPlay Download PodcastDownload

Transcription:

Scott Webb: There have been many advancements in the treatment of cancer over the past 20 years or so and that includes CAR T-cell therapy, which may seem a bit like science fiction, but is actually very much a reality. And here to help us understand CAR T-cell therapy and the benefits to cancer patients is Dr. Yogesh Jethava. He's a bone marrow transplant and cellular therapy specialist at Indiana Blood and Marrow transplantation in Indianapolis. T

This is the Franciscan Health Doc Pod. I'm Scott Webb and, doctor, thanks so much for your time. I want to have you start by giving us a bit of the history that led up to CAR T-cell therapy, and then tell us exactly what is CAR T-cell therapy.

Dr. Yogesh Jethava: There are types of hematological disorders or blood cancers, which basically need stem transplant. So the type of cancers which get cured with stem cell transplantation are something called leukemia, lymphoma and myeloma. Myeloma doesn't get cured, but you can achieve longer duration of disease control with stem cell transplantation.

Now, traditionally speaking, stem cell transplantation involves giving heavy dose of chemotherapy and followed by that re-infusion of stem cells, which are either collected from an unrelated donor or a related donor or patient himself. This is still a standard of care and stem cell transplantation process started way back in 1950s, and it is being used every year. Thousands of patients undergo stem cell transplantation.

In spite of doing stem cell transplant, a significant number of patients relapse, meaning their lymphoma, a type of blood cancer, blood and lymphatic cancer, and myeloma, a type of blood and bone cancer, comes back after stem cell transplant. Two third of the patients, it comes back.

So there are fewer options once it comes back. So what happened from 1990s onwards or from 2000 onwards, people started thinking, how do we train the patient's immune system to fight off this cancer because, that would be the best way, that would be a very natural way of taking care of cancer. And that would also be very effective because you are not putting something from outside in patient's body. You are just training their own cells. So things moved along. The initial research on this topic was done at NCI, National Cancer Institute in Bethesda and people came up with various kinds of methodologies.

So one of the things, what they thought was, why don't we take out the lymphocytes, which are basically a subset of white cells. So just to explain a little bit more here, our blood is made up of white cells, red cells, platelets. And white cells are made up of four or five different subsets. And one of the big subset is called lymphocyte. So lymphocytes are important for fighting infection and they are basically like the soldiers in our body, who go out and fight any bad bacteria or virus and they also help in clearing cancer cells. So the concept came out where the researchers at NCI harvested the lymphocytes, meaning that they took out the lymphocytes from patients' blood. And then, they modified them and created a genetically modified T-cell and reinfused those cells back in patients.

Now those genetically modified T-cells are CAR T-cells. The CAR stands for chimeric antigen receptor. The receptor is basically something which is present on the T-cells, the lymphocytes, you just modify it genetically. So it is trained to fight the cancer and you just reinfuse those T-cells back to the patient and those cells go and they fight the cancer.

So that was the concept which came to fruition. And now we have commercially available four different CAR T-cells. So a very unique fundamentally impressive technology, which has actually changed the course of disease. So patients who had no options for any treatment, now they have this novel option, and that is what the CAR T cell is.

Scott Webb: This is a really fascinating. It sounds like something out of science fiction, you know. Hard to believe that it's only been within the last 20 years, but really amazing stuff. And you mentioned patients there. So how does a patient qualify for this type of therapy?

Dr. Yogesh Jethava: So the way patient qualifies is that there are clear indications for CAR T-cells. Currently, CAR T-cells are approved in adult age group. They're approved for lymphoma, which is a type of blood and lymphatic cancer. They should have failed two prior lines of chemotherapy or those two prior lines can be one line of chemotherapy, second could be stem cell transplant. So if they failed two previous treatment modalities, then they become qualified for CAR T-cells. And they have to be referred to a stem cell transplant center. Because this is the part of cellular therapy, it comes under the broader umbrella of stem cell transplant.

So they should be referred to stem cell transplant center where a specialist in stem cell transplant and cellular therapy evaluates them and decides whether they can be suitable candidate for this kind of therapy or not because once you give the CAR T cells, there are numerous complications. And if the patient does not have good physical status to begin with, then it can be a complicating factor in their recovery. So that's why they need to be seen and evaluated by a cellular therapy specialist. And that's how they get qualified for the treatment. And most importantly, the insurance has to approve the treatment.

Scott Webb: Yeah, I assume there was another little catch there. I assume that insurance had something to do with this. And of course, nobody wants to fail the other modalities, but to be eligible, to qualify and for insurance to pay for it, this is amazing stuff. And maybe you can take us through generally speaking, what is the process for this therapy?

Dr. Yogesh Jethava: Let's take an example of patient X. So if patient X has non-Hodgkin's lymphoma. There are two types of non-Hodgkin's lymphoma. Diffuse large B cell or B-cell lymphoma and T cell lymphoma, T as in tomato. So the CAR T-cells are available only for B-cell lymphomas, B cell non-Hodgkin's lymphoma. That's why I went a little bit more in depth to explain this factor.

So say our patient X has large B-cell lymphoma. He gets diagnosed, goes to the oncologist. Oncologist starts him on standard of care based on NCCN guideline. Patient receives the treatment for say six rounds or seven rounds. He achieved good response. And then after that, patient is just monitored. Say, after a year, down the road, the lymphoma comes back, patient gets second round of treatment. He has no response. Then, the oncologist refers patients to us. We see the patient in the clinic.

Suppose our patient X is a 60-year-old gentleman in excellent physical health, no heart issues, no lung issues, no previous cancers, and does not have any other complicating factor. We decided that we are proceeding with CAR T-cell treatment because he falls into that category, failing two lines of treatment. What we then do is that we get insurance approval to proceed with the CAR T-cell.

There are two steps which happen simultaneously here. One step is to collect patient's lymphocytes, which will be trained to fight the cancer. And second thing will be to control his active disease. So both things happen in tandem. Anyhow, say insurance approves, we then decide that, "Okay, we need to collect this CAR T-cells." We. Get the patient in our clinic. And the process of collection of patients lymphocyte is called lymphopoiesis. So it's almost like a dialysis, but not dialysis, but the process itself feels like dialysis because patient sits in a chair, blood comes out of one arm. We put a big cannula to take the blood out. The blood goes into the machine. It will selectively remove only lymphocytes and rest of the blood is pushed back in the patient again. So it's like a dialysis machine. Well, not dialysis machine, but it's like the process like that.

Once the lymphocytes are collected, we send the lymphocytes to a commercial company. There are two companies, which FDA has allowed to market CAR T-cells. One is Novartis and the second company is Kite. They have products, which have the same indication, and there is a slight technical difference in the product specification. Say we send it to Novartis, the cells go to Novartis, Novartis company in their facility, in their production facility, will manipulate this patient's T-cells. They will make them active fighters. So it's almost like sending a young man for, say, Navy SEAL training. And then after six weeks, those active cells, they are shipped back to us.

Meanwhile, we keep treating patient to control his lymphoma because that, also, we don't want to go out of hand because if patient's cancer keeps growing, then after a certain stage, even the CAR T-cells might not be effective. So there is that medium balance where these CAR T-cells are really effective.

Once we know that when the cells will be shipped back to us, we get the patient in the hospital. We administer chemotherapy to prepare his body to accept those fighter cells. And then we infuse those cells through the peripheral blood, through the vein in the arm. So it's almost like a blood transfusion. And then we just wait and sit tight. And those cells, ones they're infused, they start fighting the cancer immediately.

Scott Webb: I love the analogy. First of all, I can just picture everything that you're explaining here. But I love the analogy of, you know, sending the cells basically for Navy SEAL training and then shipping them back and infusing them and letting them go to work. And, I'm wondering, what does offering this form of therapy mean for your cancer program?

Dr. Yogesh Jethava: It means a lot. So to give you a bit of a background about our program and what this therapy means is that in the state of Indiana, the size of the state, we have good number of patients with lymphoma and myeloma. And there are only two programs which has the capacity or capability to offer such treatment. And we are one of them.

We are nationally recognized for our work in this area. In fact, in the state of Indiana, we were the first to do the clinical trial for CAR T-cells, way back in 2017, 2018. Other thing is that our program is accredited by a national body to do any kind of cellular therapy, including CAR T-cells. And we are also certified by Novartis and Kite, both the companies. So both companies have to certify a center to allow them to use their product, because this is so federally regulated and important.

And it's a very high cost treatment. So the cost of product itself is close to $350,000 for Kite and $475,000 for Novartis. So that's the price of an infusion bag itself. Now you're not including the doctors' charges, the nursing charges, the inpatient stay and whatnot. That's not included. So you can imagine how costly this treatment is. That's why it's very tightly regulated by the pharmaceutical companies as well as by FDA.

So we need to get a permission from them. And we are one of the two centers in the state of Indiana who can do this treatment. So we have a large patient area and our program serves the needs for the state of Indiana very well.

Scott Webb: I'm wondering, and not that this isn't enough, because this is all pretty amazing. But what other treatment options are offered through IBMT?.

Dr. Yogesh Jethava: So we specialize in blood cancer. So our practice is tertiary care blood cancer specialty. Five doctors at IBMT. We have long experience of treating patients with blood cancers only. So we don't do other types of cancers, such as breast cancer, colon cancer. We are not a community practice. We are a semi-academic practice with all the things that you need to treat patients at a very high level.

So what all other treatments we offer apart from CAR T-cells? We offer autologous transplant. We offer allogeneic stem cell transplant. We can do transplant from the half sibling called haploidentical transplants. We can definitely do CAR T-cells. And also we have a very robust clinical trial portfolio. We have close to 16 clinical trials across all the blood cancer spectrum, which is not even available in any other place in the state of Indiana. So it's a very comprehensive high level program with a tertiary care facility. It is at par with any other university program, any other big university program. So that's what we can offer to the state.

Scott Webb: Yeah. And I'm assuming, not just even the state, you know, when we talk about local, sure, but also national. And what does your service mean? The work that you all do there, what does it mean to the world of cancer treatment both locally and nationally?

Dr. Yogesh Jethava: So cancer care is becoming more and more complex. I always say to the patients that this is not even a care. This is not something that we just do something for one day and we are going to not follow up. See, when a cancer patient walks into our facility, they become our family members to be honest with you. To give you a bit of background about what happens after the stem cell transplant or after any of this care is that patient comes once every week for at least two to three months in our facility. After that, they come once every month and then that goes on for up to a year. And then, they come once every other month for at least four to five years. So you can imagine we develop a very close bonding with the patients. They are like our family members. They bring food for us, the bring Christmas gifts, and we celebrate their birthdays when they come to the clinic. So it's a journey with a patient for us.

So that's why for the state of Indiana-- I'll talk first about our state-- so to get that kind of treatment, cutting edge treatment in the state of Indiana and to provide to the patient, that itself is a big thing because otherwise patients will have to travel way out and it's not easy for patients always to have that kind of intensive followup if they are living say a 100 or 200 miles away from the hospital. So that's where our role comes in. We provide that kind of very one-on-one care.

And second thing about nationally, so there are a couple of trial which we have, which are available only in five places in the whole United States. So we have niche clinical trials, which can basically help the patients, even say, the out of the state. So that way also, we get the referral for those clinical trials. So we have a comprehensive service, which helps locally, as well as to the patients out of the state with clinical trials.

Scott Webb: Doctor, as we wrap up here today, why should someone come to Franciscan Health to receive cancer care?

Dr. Yogesh Jethava: That's a question, which has a lot of answers, but let me explain you something. At IBMT, we treat patients as our family members. When a patient walks into my clinic, I will treat them exactly how I would like to be treated. My brother or my sister or my aunt or my mother or my father, that’s exactly how I will treat every patient. And that's our motto at IBMT. That's the first thing.

Second thing is that our practice, even though it is such a sophisticated cutting-edge high-level practice, it is run entirely by the doctors. So a lot of the universities have nurse practitioners, clinical fellows, not that it is a bad thing to have them. However, when you have to go through three or four layers of people before reaching a consultant, the message can always get a little bit distorted or a little bit diluted. In our practice, if a patient calls at nighttime, they will talk to me or to one of my partners. So there is a direct patient involvement, which obviously patients love, because they know that they're willing to talk to a doctor, a treating doctor and not just a fellow or nurse practitioner who is on call. So that's the second thing.

Third thing is that we have a very collaborative approach with our local doctors. So whenever, say, a doctor from state of Indiana refers a patient to us, on the same day, we call the doctor. We let them know we saw this, this is the plan. Patient will be coming back to them in a week's time. They have to make sure that these things are done. If any questions, this is my cell phone. So we have this direct communication. We don't rely on any intermediaries. We don't rely on any bureaucratic process for the patient care. So that makes it very easy for the patients, for the referring doctors. They know their patients are in the safe hands.

So this is the biggest plus point. In my 12 years of professional career, I don't know any other practice which has this kind of direct patient care involvement with the patient and with the referring doctor. And that's why our practice is one of the best in the country. It is certainly the best in the state of Indiana. Our outcomes are good. In fact, they are at par with any other national hematologist service, and that's why we would like patients to come to our practice.

Scott Webb: That's a great way to wrap up. You know, cutting edge work, open lines of communication, family approach, many good reasons to seek care at IBMT. Doctor, fascinating conversation today. I think I could just talk to you all day, but we don't have that kind of time, but thank you again. And you stay well.

Dr. Yogesh Jethava: Thank you very much, Scott, for your time today.

Scott Webb: To learn more about the IBMT program, contact the Indiana Blood and Marrow Transplantation office at (317)   528-5500 or visit FranciscanHealth.org/car-t-cell-therapy.

Indiana Blood and Marrow Transplantation in Indianapolis is one of only two programs in the state of Indiana offering tertiary care for hematological disorders, blood cancers, including bone marrow, stem cell transplants and CAR T-cell therapies. IBMT specializes in the treatment of leukemia, Hodgkin's or non-Hodgkin's lymphoma, multiple myeloma and other malignant blood disorders.

Our nationally recognized experts at IBMT have more than 20 years of safely conducting these procedures and IBMT is accredited by the Foundation of Accreditation of Cellular Therapy. And we have unique experience and training in managing patients with complex blood conditions. And we hope you found this podcast to be helpful and informative. This is the Franciscan Health Doc Pod. I'm Scott Webb. Stay well, and we'll talk again next time.