Hannah Loosle (00:12)
Hi everyone, welcome to today's episode of the Health Tree Podcast for Lymphoma, where we connect patients with lymphoma to the research and information they need to know about. If you've been with us before, welcome back. If this is your first time joining us, welcome. We're so happy to have you join our lymphoma community. My name is Hannah Loosle. I'm your host and Lymphoma Education Manager here at Health Tree Foundation.

The goal of this podcast is to make research and new information coming out about your disease easy to understand and easily accessible. If you've ever found yourself overwhelmed by clinicaltrial.gov or a medical abstract, we are here to change that. Stick around until the end of the episode when I'll be back to share my final thoughts on today's interview as well as some additional resources you can dive into related to today's talk.

The topic of today's podcast is the latest advancements in CAR T therapy for B cell malignancies. We are joined by Dr. Ehsan Malik, the Director of Translational Research for Multiple Myeloma and Interim Head of Chief of Lymphoma at Roswell Park. He specializes in an array of plasma cell disorders and his focus is on developing novel cellular and immune-based therapeutic strategies.

That promise improved outcomes and an enhanced quality of life for patients. I chose Dr. Malik and the topic for today's episode because 2024 was a huge year for CAR T advancements for lymphoma and 2025 has many new and exciting things on the horizon. And now without further ado, let's bring on Dr. Malik.

Hannah Loosle (01:45)
welcome Dr. Malik. Thank you so much for joining us today. I'm really excited to dig into your research and some of the recent advancements in CAR T therapy for B cell malignancies today. So I wanted to start with a high level overview. So was wondering if you could tell us what CAR T therapy is and how it's transforming cancer treatment.

Ehsan Malek (02:07)
Thank so much, Hannah, for having me. It's a privilege for me to attend this podcast. Health Tree is very close to my heart. We work very closely with Health Tree Myeloma Foundation and people to conduct some research. And I think I'm very supportive as well as optimistic with your effort in this area. My name is Ehsan Malik.

I work at Roswell Park Cancer Center. I'm a director of translational research for multiple myeloma as well as interim chief for lymphoma section for now. primarily my focus is cellular therapy and specifically CAR T cell therapy If I want to make it in the nutshell what CAR T cell is, we need to understand this in the context of

What is cancer and what really fuels cancer? What fuels cancer is lack of recognition by immune system. Essentially, myeloma patients or let's say lymphoma patients, their immune cells is unable to recognize cancer cells. And cancer cells, have mechanism to escape from this recognition. Therefore, even many of them, have

competent immune system or close to competent immune system, still disease progress. Therefore, we have to give them chemotherapy, essentially poisons to kill cancer cells. In CAR T-cell, we take immune cells, the main immune cells in our body is a T-cell, circulating T-cells that are in peripheral blood. We take immune cells and we genetically engineer that in the way that it can recognize cancer cells. And we

gift it back to patients. So this enabled immune cells, they are able to recognize cancer and kill cancers on ongoing basis for example, for myeloma for a couple of years for lymphoma, is chance of cure even with this therapy. And importantly, there is no need for ongoing chemotherapy, ongoing poison to give to patients. That's very important. And

how we do that. So immune cells or T cells, when we take them, we genetically engineer that in the way that can recognize a target on myeloma cells. So the first target we have available for myeloma is BCMA, B cell maturation antigen for lymphoma. have CD19 primarily. And so we are genetically engineered these T cells in the way that they can attack

any cells that they have these targets on them. And this really enables to provide a very effective therapy using patient immune system without much chemotherapy side effect. This is very important. And the side effect that we are dealing with CAR T cells they're temporary and they're not mostly permanent. There's no cumulative toxicity like ongoing treatment. So in not sure if I want to answer your question.

Yeah, CAR T cells essentially enable the immune system to recognize cancer cells and attack them is a new generation of immune therapy. The older generation of immune therapy, their checkpoint inhibitor that not very specifically, they stimulate immune system. But CAR T cells is very target, very precision medicine, essentially for cancers.

We have

Hannah Loosle (05:26)
Thank you for that

wonderful overview of what CAR T therapy is. And I know that Roswell Park is a leader in the field of cellular therapy. So.

I wanted to hear just a little bit about Roswell Park's journey in cellular therapy and what sets it apart as a leader in the field.

Ehsan Malek (05:44)
Roswell has a very long track history of leading different therapies for, especially malignant heme. If you go back to 2012, Phil McCarty, he led CLGB trial that it was relevant with maintenance. for the CAR T cell arena, we mainly, we have different avenues that many cancer centers, they have what differentiate us from.

many cancer centers is we are building a very solid infrastructure for manufacturing CAR T cells. There is a, we have a GMP and good medical practice facility. are there essentially certain standards that from FDA has to be met to be able to manufacture CAR T cells that can be delivered for human and human treatment. So we have a massive infrastructure for that. And that really is very important because

is enable us to production of CAR T cells in-house production of CAR T cells. And this is very important because we can generate cutting edge technology, carti in-house, it's not significant amount of time rather than collaborate and be dependent on the third party as well as cost. So we are really positioned ourselves in a very strategic point.

for collaboration with a variety of industry as well as other cancer centers. also one of our initiative is expanding access to CAR T cells. CAR T cell I think is very important that it works for myeloma, lymphoma, leukemia, and as well as I think solid tumor is emerging, but still we have problem with a minority, underrepresented minority that they have problem with access to.

the I've noticed in West New York, are having many of myeloma patients or lymphoma patients that they could get CAR T cells. They don't because in the community, in the small practices, they get other therapies, for example, by specifics before getting CAR T cells. And when they come to us is

Hannah Loosle (07:48)
you

Ehsan Malek (07:51)
harder to generate CAR T cells and outcome is suboptimal if they are exposed to long-term bi specific. So really we want to fill gap in the knowledge for physicians as well as patients that CAR T cells should be moved earlier in therapy. Really we want to have the best outcome. So this is very important that

Hannah Loosle (08:06)
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Ehsan Malek (08:17)
We educate patients. We reach to patients that really they may not have access to a tertiary cancer center like the Roswell. So we have an initiative with allo CAR T cell

that we will talk about that I believe that caught the manufacturing time. So we deliver CAR T cells for patients that really they are need and they don't have much time because they were not referred on time. And

This is a CAR T cells from healthy donors that it has pros and cons and it's a very attractive strategy. So at Roswell, would say we are tapping in the area that really it puts Roswell as a destination for CAR T cells for malignant heme as well as solid tumors. We have a very active design section for a small cell lung cancer melanoma.

GI cancers that ongoing trials we have as well as a standard therapy if they approve cellular therapy.

Hannah Loosle (09:14)
Wow, you are really doing a lot of amazing work at Roswell Park. I really appreciate that you're looking into making sure patients can access CAR T because I know that's a huge problem with CAR T therapy and some of these new therapies. And then I also wanted to talk about some of the recent advancements from, you know, 2024 in CAR T therapy. So what would you say are some of the most exciting breakthroughs in CAR T from 2024?

Ehsan Malek (09:39)
Yeah, 2020 for many people they take I think that was an explosion for artificial intelligence and you know all these LLMs and so forth but I think for CAR T and also it was a very important year in terms of variety of aspects one of them was I think there is a very massive effort nationally in multiple large cancer centers to innovate measures to

increase CAR T cells persistence. That's really important because patients go through CAR T cell manufacturing and then be administered. pass the safety period of CRS and ICANS and so forth. And it's very important to keep CAR T cells as much as possible in circulating CAR T cells in patients' bodies. So there are a variety of efforts from, for example, the

making more memory cells CAR T cells, administer CAR T cells with small molecules, with checkpoint inhibitors, and all of those I think it will translate to a very important milestone of CAR T cells that I think the future of myeloma patients, it will look like CAR to CAR to CAR rather than continuous chemotherapy. I think 2024 we could

feel this prospect to some extent that, for last 20 years, last 15 years, at least in practicing is the continuous therapy for myeloma. will mean it has been the main theme of therapy that if you have transplant, still you need maintenance. If you start Darzalex pamaldomal, you stay on that until you have relapse and you change treatment, you stay on chemotherapy forever. So

Hannah Loosle (10:59)
you

Ehsan Malek (11:21)
CAR T cell is a very important modality that comes to horizon and give one time treatment with a long treatment free period. For example, for CAR vectin nowadays, PFS, you know, reach 34, 36 months, 50%. So with 50 % possibility, you have three years of remission for patients without any ongoing therapy. So, and future will looks like that.

you go as myeloma patients, go to CAR and then stay in remission. You relapse and then change the target of CAR T cell for, for example, BCMA to GPRC5B. You stay three, four years in remission and then change the target again. So CAR to CAR to CAR rather than continuous therapy. For lymphoma also, think CAR T cell, especially when applied earlier, it could result in curing good

slice of patients. So that's the new things in 2024. Another important thing, I think, across the board is happening is off the shelf CAR T cells. We had the allogenic BCMA CAR T cells trial that I think has a very impressive result. And even result is the same as auto still from logistic standpoint and market coverage to reach underrepresented

Hannah Loosle (12:19)
you

Ehsan Malek (12:48)
patients is very important. Why is that? Because for normal CAR T cell for FDA approved, currently FDA approved CAR T cell, we use patient T cells. And then patient by patient individually, we have to manufacture CAR T cell. So that takes six to eight weeks sometimes that I take T cells from patient and then I have to do a bridging chemotherapy to keep the disease into some sort of shape until CAR T cell is

available and is ready and go from there. So this individual manufacturing is very expensive as you imagine and it's time consuming and from biological standpoint, patient T cells are still, because of continuous chemotherapy they were very exhausted. This is the term that we use many times in immune therapy, exhausted T cells. Means that T cells are not

robust. If you build CAR T cell out of that T cells, they don't have that much tumor killing property. So when you do allogeneic CAR T cell means that you take T cells from healthy donor, a young healthy donor and make a CAR T cell off the shelf. You make massive amount of CAR T cell. So you have a ready CAR T cell. you get, if I get the referral from CAR T cell, let's say 40 hours from Buffalo in West New York.

that is very common. I don't have to, you know, refer back patients to primary to bridging therapy and micromanage bridging therapy and make sure that all the dates is fine and all. I can just admit the patients and give CAR T cells. That's it. So that's off the shelf. think it was an allogenic platform is the one of the biggest advancement in 2024 that we realized that is doable because

Before that, as you can imagine, if you give T cells of another person to another person, we could have a graft vs host disease We could have a rejection. And that was the hypothetical safety issue that we really, with the CRISP technology that they are using, the GVHD rate is zero. so that proved realistic, and that's very important.

There was a great presentations from variety of cancer centers that they proved that dual targeted therapy and triple targeted therapy has a reasonable safety signal. So that's, that's another one that we are really impatiently.

waiting for that to really see if this approach can result in the eradication of myeloma. So that's essentially, here I think another one also was a confirmation of the real world data of the CAR T cells is very promising idea that for CAR T cells trials, we naturally organically, we have to cherry pick because we recruit untrialled patients that they have different...

adequate organ function and patients, can wait. So the idea was, well, it may not represent real world, but the data from both CAR T cell BCMA, as well as lymphoma trials shows real world data is very comparison for trial. So that's, I think it's encouraging for patients. 2024, yeah, it was a very positive year. Many questions that we were doubting in the answers.

We had a very confirming answer.

Hannah Loosle (16:08)
Yeah, that's great. There was a lot going on in 2024 for CAR T. And were there any specific CAR T advancements at Roswell Park in 2024 that stand out to you?

Ehsan Malek (16:20)
Yeah. So in Roswell, are basically, the goal is, the main goal is expanding access. think is the main goal. CAR T cells is a proven therapy for myeloma and malignant heme lymphoma leukemia. It has reasonable safety and very high efficacy, especially highest efficacy in myeloma, more that least that we have.

since beginning of, I would say, melphalanine, highest efficacy single agent, single therapy that we can deliver. think expanding access is the best one. One of the efforts that I Roswell had and patients they had very high benefit from that was allogeneic CAR T-cell. So these T-cells, they are from healthy donors. As I mentioned, there's a very cutting edge genetic

techniques called CRISP that you can take T-cell receptors out of T-cells. So when you take T-cell receptors out of T-cells, these T-cells, cannot cause graft-versus-host disease. So the T-cells they were taking from healthy donors genetically engineered that with this CRISP technology to take T-cell receptors and eliminate chance of GVHD and then be

had the BCMA CAR installed on them. So you have allogeneic off the shelf and mass produced that in billions of billions for let's say 500 patients or even higher. So you have an off shelf that, and I think that's the promise of the cutting the cost significantly because one of the problem with expanding access is cutting costs. Although,

Personally, think insurance companies, they understood this, that the cost of continuous therapy may be even higher than CAR T cells. But still, if we could curb the cost and the timing, manufacturer timing, that I have many patients that they come to me, they are not ready for CAR T cells. They have to give bridging therapy. They have to wait for manufacturing CAR T cells because we are using their own CAR T cells.

Hannah Loosle (18:25)
you

Ehsan Malek (18:32)
So we had patients that really these products could save their life because they ran out of options for managing therapy. They could not wait essentially. I think that was one of the best outcome we had for Roswell in 2024. Always safety also is one of our mission. Cartycella still can have a toxic side effect that

Hannah Loosle (18:50)
.

Ehsan Malek (18:54)
can impact life. Generally speaking, luckily it's temporary, it's not long-term usually, and it doesn't have cumulative effect like chemotherapy. I think we had a much better management of CRS and ICANs in terms of just, I think, the matter of experience, the matter of we could predict who's going to run to high toxicity ICANs and...

CRS based on ferritin and CRP. We have data around that as well as we noticed that disease volume is very important. think nationally, this is the main theme that disease volume before CAR T cells is very important to limit the CRS and I can side effect of CAR T cells. If you have a high disease volume, there's a very high chance that we may run to neurology symptoms too.

Hannah Loosle (19:32)
you

Ehsan Malek (19:47)
and CRS. And we noticed that CD28, endogenous CD28 and CD86, that they are on myeloma cells. They could be basically mediating this disease volume relationship with high CRS and ICANs. Therefore, any patients comes to me in terms of I want to have lowest disease volume before we go to CAR T cells. And it translates to significant, I would say,

easier route for CAR T cells. We have much less ICANs and CRS. we do that, I think another aspect of CAR T cells in 2024 is that we noticed that if we make less inflammatory CAR T cells, are different ways to do that. Less inflammatory CAR T cells, we can eliminate or eliminate some of the high-grade toxicity as well as

Hannah Loosle (20:14)
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Ehsan Malek (20:37)
you know, decrease general rate of CRS and ICANS. How we do that? By now, choosing more memory cells rather than active cells. This is very important. We have ways to manipulate CD4 to CD8 ratios. There is promise of NK. CAR also is coming that is very important. I don't think we should underestimate that. Another aspect of CAR T that I think is very important to understand that

we nowadays we having safety switch. So when we examine new CAR T cells, new targets, for example, dual triplet, always there's a danger. These are, you know, during infancy, would say CAR T cells, there's a danger that toxicity can be out of hand. And it's very important from safety standpoint that you have a switch to kill CAR T cells or detune CAR T cell. can manipulate the idea that

We're going to give CAR T cell and just watch it and see what happened. It's kind of an old fashioned. Nowadays we want to have the switch, a safety control switch that if really causing problem, we can shut it down. And that's very important it's a stepping stone essentially to be brave, be targeting more targets and so forth, because you have a safety switch that you can turn it off whenever you want, rather than you don't have any control. So I think,

There is a lot to do in this arena. And I think 2024, general speaking for entire country, entire world. And Roswell was a very good positive for my lymphoma patient, as well as general in malignant he me lymphoma. had a great turnout in terms of the outpatient delivery of entire CAR T cells. So nowadays, know, safety toxicity, safety profile is so manageable.

we can apply a CAR T cells much earlier in therapy when the disease volume is not that high. So we are able to do outpatient. That is again, comes with patient access, easiness of the administrating CAR T cells and so forth.

Hannah Loosle (22:39)
Yeah, that's amazing. You know, as I mentioned, Roswell is doing so much wonderful work with CAR-T and cellular therapy and

I think 2025 will be another big year for CAR T like you've referenced. So I want to talk about some of the things that patients can look forward to in 2025. So what new possibilities or applications of CAR T do you see on the horizon for 2025?

Ehsan Malek (23:04)
Yeah, I think, CAR-T is still in infancy. And 2025, I think the main news will be expanding CAR-T cells to solid tumor. You know, if you want to compare solid tumor and malignant hematology, solid tumor, they're around, I would say, estimate 60 % of general cancer, speaking. So really is impacting higher ratio of populations and so forth.

there's an unmet for, know, terminal stage stage four lung cancer, melanoma, and all of those. So I think it will be nice if we could have a positive signal that I think we will for some of the solid tumors. Solid tumors, generally speaking, has a very immune suppressive microenvironment. It has shield. It has lots of connective tissue that protect that from CAR T cells. So

the different maneuver to break this shield, just break the immune suppressor in microenvironment is very important. think that's my hope because that would be the beginning of the new era really for enabling immune system to see cancer cells in a very precision way. We haven't had this type of therapy. think the, another aspect, another front could be combination therapy for CAR T cells. So.

How the question is how we can prolong survival of CAR T cell. One of the main approaches, checkpoint inhibitor that has been immune therapy since let's say 10 years ago or so, even longer. So how we can apply these checkpoint inhibitors with CAR T cell to enhance efficacy of CAR T cell as well as prolonging survival that can translate to longer remissions for a variety of disease for mainly

malignant heme myeloma lymphoma as well as solid tumors. Solid tumors we see, especially for example, for a small cell cancer, we see some change in tumor, but it goes away and tumor escapes. So the question is how we can really combine CAR T cells with other agents to increase efficacy and prolong the remission time. Another one is faster and more affordable access to CAR T cells. Again,

These innovations, are very fancy, they are very exciting. However, when you want to translate to society, the question is who's to pay for all this? with the economy that right now we have, the idea is our GDP portion of the health care less is the same. However, the innovative therapy for medicine is getting more expensive and more expensive. At some point, we're going to have, at least we have right now,

we have access issues that patients that they don't have a good insurance. Some of the insurances, you know, may have hard time to cover this expensive service. So if really we want to expand access, we have to decrease the cost. And one of the main things that I think Roswell is doing that, that generating GMP facility, the infrastructure that we have, it enabled us to escape from industry high

pricing and we can manufacture CAR T cells in our facility, run clinical trials independently, independent of the finance of the regular market. So that's really, think, the best things that patients at Roswell, they can benefit from that. As I mentioned, the strategies such as allogeneic CAR T cells is the main things that

Hannah Loosle (26:26)
.

Ehsan Malek (26:32)
For example, CAR T cells auto for myeloma, it costs around half a million dollars. If really we manufacture mass manufacture from off the shelf therapy type of mindset, it can decrease significantly and we can deliver these therapies to higher number of patients. think

patient experience standpoint, it draws well, it will be a very good center in this New York at least that cover, you know, adjacent states to a very wide area of the patient population that we bring cutting edge, immune therapy, next generation of immune therapy for wide variety of patients.

Hannah Loosle (26:59)
you

it sounds like there's a lot to expect in 2025 for CAR T therapy, so that's really exciting. And you mentioned this a little bit already, the expansion of Roswell Park's GMP facility. Can you tell us about the purpose of that expansion and, you know, a little bit more about how that will impact research and treatment capabilities?

Ehsan Malek (27:39)
Yeah. So, cellular therapy is a very expensive therapy. Why is that really? Because we have to manufacture cells rather than manufacturing a small molecule in massive amounts. And when you deal with cells, human cells, and you want to manufacture, manipulate it in different ways, let's say,

and giving back to patients, this needs very high standards, very high biosafety standards that FDA has a very high standards for this called GMP and good medical practice facilities. To make those facilities, you need a variety of expertise essentially that it goes to this process.

is a main bottleneck essentially for academic centers because academic centers, we have targets, we have ideas that we want to combine CAR T cells with these agents and so forth. However, when we are dependent on drug company that, you know, they look at their prospect that, okay, well,

we're going to bring this CAR to market and this is going to be margin and so forth. is different work from academia. there's an unmet need to feed this requirement for academia that they should be able to make their own cellular therapy or CAR T-cell, let's say. And for doing that, we have a lots of investment. If you say,

I think we have 14 or 15 GMP units right now that we can manufacture and feed many clinical trials, whether in Roswell or different sectors. Even we can provide CAR T cells for industry for companies that are not able to do this GMP facilities and so forth. So I think this

is as I said, is a bottleneck for research in cellular therapy and we are open to business essentially. And so you're going to hear more about Roswell, I think in next five years as a one of the mecca of CAR-T and cellular therapy in general,

Hannah Loosle (29:42)
.

That's great. I'm very excited to see this new facility and all the great things that come out of it. And now I want to talk a little bit about the patient experience. So how does CAR T therapy compare to traditional treatments like chemotherapy or radiation?

Ehsan Malek (30:07)
Yeah, so CAR T cells is a very high precision medicine, if you say. Why is that? As I said, you recognize a target that is only on cancer cells or almost only. For example, BCMA is exclusively on plasma cells and plasma cells is the origin of multiple myeloma or CD19.

most of the lymphoma that are CD19 positive and CD19, they are not present outside of B cell lineage, if you say. So for B cell malignancies, CD19 and BCMA turn out to be very well target. When you come to chemotherapy, whether it is conventional chemotherapy that essentially is poison to kill all fast replicating cells or radiation that is same phenomenon,

You don't care about whether it's cancer cells or not. You kill all fast replicating cells, whether this is a bone marrow cells that make our red blood cells or white blood cells, whether it is hair follicle that we're going to lose our hair or is gut mucosa that we're going to have, you know, GI problems and so forth. So this is the still, would say still we need radiation, still we need conventional chemotherapy.

This is a new era. We are using those old therapies. Minimum is necessary really, but I think year by year our dependence on those will be decreased. We have immune therapy also such as checkpoint inhibitor and so forth that they are not that much precision medicine. They stimulate immune system against cancer cells in general.

they may or may not work. are not that much specific. They're different than CAR T cells. So CAR T cells is a new generation of therapy. And I mentioned CAR, for example, for my lung patient in a new era, because I had one of my close patients that, you know, he's very close to my heart. He had my lung in last 12 years. And he was telling me we did a CAR T cells, I think, two years ago. And right now it still is in remission.

He was telling me he's a very high performing, you know, in finance and so forth, travels a lot. And in 12 years, it always, he was dependent on infusion room that he has to come to infusion room, get something or get the chemotherapy pills. Always there is no free lunch chemotherapy. Always there is the side effect. And when you go to infusion room as a cancer patients, as a provider, sometimes we don't notice those aspects, but

from a patient standpoint, it can be very taxing actually that every time you go to infusion room, it reminds you you have a cancer, you make friends there with patients and so forth, they may lose their life before you. So these are lots of emotional and taxing that goes on the patients. And if really you can graduate a patient from infusion room and tell them next three years, you don't need any chemotherapy.

You just come to me every two months, three months, whatever. We just check a lab. can check a lab, other side of the world. You don't have to come to me. This is a new lifestyle for my normal patients. This is a bright day that, you know, they haven't had experience. So this one time treatment, the treatment free period is a new paradigm that is changing, I think, field significantly. And that's the difference.

between CAR T cells and specific. Essentially, bi specific, there are agents that they bring patient immune cells to cancer cells. They don't manipulate or enable immune system, immune cells. They just bring immune cells next to cancer cells. when you do bi specific, first of all, is ongoing treatment. So always you have to get something. And second of all,

Hannah Loosle (33:50)
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Ehsan Malek (33:56)
you have very high risk of infection that cumulative increase to 70%, 65 % grade three infection. Grade three infection is an infection that, you know, most likely you may end up in the hospital is a very, have to stop therapy and long antibiotic therapies and so forth. So there is a very high risk of long-term and cumulative risk for specific and more importantly, if you're exposed to bi specific for long-term.

we cannot make CAR T cells, quality CAR T cells after that. So it's important that patients get CAR T cells before any bi-specific or any long-term bi-specific, I would say. So CAR T cells differentiates itself from bi-specific from this one-time treatment that from even healthcare costs, if you graph the, I mentioned that CAR-T with current agenda have very high costs that hopefully we can decrease it.

However, with this even high cost at the beginning, if you map the patients that did CAR T cells and three years in remission versus the patients that has continuous chemotherapy, whether it is bi specific or dorsal X-Base or sarclis base or any of those, you still have very comparable cost, even lower cost. Even you're not capturing the amount of time that patient lost from work.

the amount of time that they didn't have for family. These are important things that we don't have a capture match. We cannot capture it in the numerical value. So, but if you have in trials, example, clinical trial, prospective clinical trials, compared CAR T cell versus continuous therapy, when you do essentially patient reported outcome, lifestyle assessment drastically is different and stays different.

throughout the therapy. This is very important in CARTITUDE 4, in CARMATRI, in lymphoma trial, all of them invariably, when they assess quality of life, quality of life in CAR T cell, very meaningful is different. So I would say CAR T cell, most of the side effects are temporary, they are not permanent, they are not cumulative. That's the main difference between chemotherapy. For radiation also is important. you

exposed patient to long radiation, your quality of T cells is not as good as no radiation. So radiation, mean, many times we have to do that for patients, local control, for pain control and all of those. And we still use that, but we should keep in mind that really if you want to have happy T cells and have a happy CAR T cell,

we should minimize radiation, should minimize classic chemotherapy, cytoxone, melphalan, bendamol, all of those that is very important. So overall, I would say from patient experience, it's night and day in terms of continuous, always you come get some poison versus carcicillin. I enabled your immune system to attack cancer.

Hannah Loosle (37:00)
Thank you for that. I really appreciate you touching on how CAR T impacts the quality of life and how taxing other treatments can be and how, like you said, it's a night and day difference between the patient experience for CAR T.

Ehsan Malek (37:00)
Yes.

Hannah Loosle (37:16)
And I was wondering if you could also talk a little bit about what the most common side effects are of CAR T, how serious they are, and how they're typically managed.

Ehsan Malek (37:25)
Yeah. Generally speaking, CAR T cell, they have two major side effects. One of them is cytokine release syndrome or CRS. Essentially when we genetically engineered this CAR T cell, there is a genes that we put in T cells that enable T cells to propagate and replicate and stay in the patient's body for a long time. That propagation and replication, it can cause that inflammatory response in patient.

patient's body feels that they are picking up a cold, example, they have fever, tired, sometimes high breathing, high heart rate and so forth. So they call it CRS. Usually depends on the target, depends on the product, what memory type or active type CAR T cells we use, but usually happens in the first week, I would say. And nowadays we have a good medication called tocilizumab, it's an interleukin-6.

pathway inhibitor that really we can control that. Sometimes we have to do short term steroids that the study showed short term steroids really does not compromise efficacy. So we use these agents more liberal and more importantly, timing of that, that we can predict. Nowadays we do CAR T cell where most of the application outpatient. and make it much more pleasant for the patient.

Another category is ICANS immune cell associated neurotoxicity syndrome that knows also, although exact mechanism is not known, but the rapid robust CAR T cells replication caused that. So if you have a good response to CAR T cells, it's very likely that you may have ICANs also.

different product of CAR T cell CD19, BCMA, lymphoma, and myeloma. They have different percentage, but usually 10 to 15 % or I would say 7 % to 15 % or so is varies. Usually happen first two weeks. The median time usually is longer than CRS for five days. We treat them with steroids to control this propagation of T cells. And most of the time,

is very reversible, how it present. Most likely patients will have tremors, sometimes memory loss. For example, if I tell patients five words and ask them to repeat, they may have hard time. We score these ICANS based on different neurologic domains, assessment, and on daily basis, these ICANS score should be recorded by nurses or patient caregivers.

we can proactively act upon that on the earliest stage. So these two main is share almost on all CAR T cells. There are CAR T cell specific side effect. For example, for BCMA, you have a long term cytopenia that is very well known around 30, 40 % of patients they have. Cytopenia means that low blood cell counts, white blood cell counts, and red blood cells as well as platelet longer than one month.

Nowadays we can do stem cell boosts for patients. In fact, we did a Markov model to assess how cost-effective it is to collect extra stem cells for providing boosts for those kinds of patients to limit infections and hospital admission. It actually is very cost-effective. Other than cytopenia, CRS and ICANs,

There are, for example, Carvykti we may see late neurologic presentation. For example, Parkinson's type symptoms, tremors, shuffling gait, and the lack of expression on the face, on the muscle, on the face. It can happen three, four months after Carvykti a few percentage of patients. So these are things that keep in mind, but overall speaking, 95 % of patients,

and they go to a temporary and reversible side effect. There's not much long-term side effect and cumulative side effect. And I tell patients that you invest, you know, let's say one month and we have to check on you very frequently. But when you recover from all of those, with no treatment, your cancer is in deep remission. And that's the art of CAR T cells.

Hannah Loosle (41:39)
Thank you for sharing those side effects. And I know you've mentioned that there is a lot of work still being done at Roswell Park, a lot of ongoing clinical trials and things like that. So patients want to...

Learn more or get involved in CAR T clinical trials at Roswell Park. Where can they find more information or who can they contact?

Ehsan Malek (42:01)
I think the best resources for Roswell trials for patients in West New York, Pennsylvania, Ohio, and so forth is the Roswell website, essentially. have all of our trials, especially CAR T cell. They are clinical trials.gov also. least all of those, you search Roswell CAR T cell, let's say lymphoma, it lists

We should list all of the CAR T cells trials. We are open. We can see patients sometimes less than a week, not later than two weeks, any type of referral, any type of self-referral. If you want to be evaluated at roswell for lymphoma in any stage of therapy, don't be shy really that CAR T cells may not be for me. If you're on a continuous therapy for lymphoma, CAR T cells most likely apply to you.

So feel free, you can call Roswell. We will see you less than a week, less than two weeks at maximum. And we evaluate and we get to your primary oncologist if you like and we coordinate a treatment plan that suit, you know, specific needs of your disease, your lifestyle, your social needs and so forth.

Hannah Loosle (43:15)
Perfect. And do you have any final messages that you would like to share with blood cancer patients and their families about CAR T and the work being done at Roswell Park?

Ehsan Malek (43:22)
So, thank you.

First all, I'm privileged. Thank you so much from HealthTree from what you do from, I feel really, I support your effort in cancer space. I encourage my patients to get on HealthTree to share their lab and clinical course with HealthTree because this is the way that we can make difference. For blood cancer patients, I think

My main message is stay tuned, don't be disappointed. There gonna be a massive advancement in malignant heme and blood disorders in next couple of years in myeloma, in lymphoma, in leukemia,

I think CAR T cell is in advancing as a basic principle of that that enable your own immune system to see cancer cells and kill them. That's differentiate that this error with the previous error. And really I hope to we see someday cure for incurable malignant hematology disorders such as myeloma, some of indolent lymphoma, obviously follicular lymphoma and so forth.

And I think CAR T cells, it may get us there. This is, you know, unprecedented, this amount of effort, this amount of different avenues and pathways that it can result in a kind of a revolutionary treatment. I'm kind of optimistic to use this kind of words, but it may, we may get to the prime time. And I really hope for the best. And my

message for patients malignant and inpatients is, you know, it's not easy. I don't have a cancer. None of us providers have cancer. You have cancer. We are here to meet your needs and I hope for the best we provide. like to provide the most cutting edge CAR T cells therapy in the world and you are in right place.

Hannah Loosle (45:15)
Thank you so much for that message. And this whole interview has been so informative and helpful for patients. So thank you, Dr. Malik for joining us today and sharing about the incredible work being done with CAR-T.

Ehsan Malek (45:28)
Thank you Hannah for having me. Have a good day.

Hannah Loosle (45:33)
I loved this interview. So much happened in 2024 and we can expect even more great things for CAR T in 2025. I really appreciated the work that is being done to increase access to CAR T therapy, which will help so many more patients receive this life-changing therapy. It was also great to hear about the patient experience with CAR T and how minimal the side effects can be compared to other common treatments. I thought it was so interesting to hear Dr. Malik's perspective on what we can expect going forward.

and how CAR-T might be expanded to solid tumors and other types of cancer in the future. If you want to keep learning, we have some additional resources you can look at related to today's topic. We have tons of CAR-T webinars, news articles, and Health Tree University videos on our website. Thank you so much for joining us today on the Health Tree Podcast for Lymphoma. I hope you learned something new. And join us again next time to learn more about lymphoma research and what it means for you.