Darrin Godin: Hello and welcome to Talking Hope. I'm your host, Darrin Godin. Today I'm pleased to be speaking with Dr. Tanya Siddiqi, a renowned hematologist-oncologist and the medical director of lymphoma for City of Hope, Orange County. Dr. Siddiqi specializes in diagnosing and treating blood cancers, particularly chronic lymphocytic leukemia, also called CLL, and B-cell non-Hodgkin lymphoma. In addition to her clinical practice, Dr. Siddiqi is the principal investigator on numerous clinical trials evaluating the role of targeted therapies including CAR T-cell therapy and other novel agents. Dr. Siddiqi practices at City of Hope, Orange County Lennar Foundation Cancer Center, where she is part of a team leading next level cancer research, treatment and research. And Dr. Siddiqi, I am so excited to have this conversation with you today. Thank you for your time and welcome to Talking Hope. Well, I'd like to start with finding out a little bit about why you decided to pursue medicine and what led you to specifically going into oncology.
Dr. Tanya Siddiqi: So it's not a very dramatic story. I grew up in Pakistan, and in Pakistan there are a little bit limited options in science. And when I was in high school trying to pick subjects for what I wanted to do in the future, my dad, who's a banker by profession, just gave very common sense advice that, "Hey, pick stuff that you enjoy doing and you're good at because this is what you're going to be doing for the rest of your life." So I enjoyed biology, I was good at it, an A student in biology, so I just kept going towards the pre-med route because in Pakistan there wasn't much else you could do with biology and science in that sense, bio and chem. And so I ended up in med school for that reason. Enjoyed it thoroughly. It was tough. Made some great friends, met my husband, the whole sort of journey.
And the very first clinical mentor I had in med school... In Pakistan, it's five years of medical school, and in the third year we start our clinical, clinics and hospital rounds and whatnot. And the very first mentor I had was a hematologist-oncologist, and he set such a great example of what a professional position should be and just created this... Just shared his love of blood and everything blood, meaning blood cells and just the biology of and physiology of the human body where hematology was concerned. Just right from the get-go, I was hooked and I knew I wanted to do oncology because that was the next step to get to more hematology. And so then I pursued hematology-oncology research and here I am today.
Darrin Godin: And here you are and this is the thing you do day in and day out as a physician scientist.
Dr. Tanya Siddiqi: That's correct.
Darrin Godin: So I'm going to ask you a question that I normally ask toward the end of our conversations. But you work for City of Hope. What does the concept of hope mean to you, Dr. Siddiqi?
Dr. Tanya Siddiqi: So it's always hard to describe hope because it's so many different things, but strictly speaking, hope is sort of a feeling or expectation of a positive outcome, right? Something that's ending the way you want it to end, whether it's a story, whether it's an event, whether it's a disease, whether it's whatever it might be. And for us at City of Hope and me especially, that is my understanding of it, that I want to be able to provide that positive outcome for a patient, even if it doesn't mean you're winning the battle against cancer, but maybe it means you're comfortable. Maybe it means you've met all your life goals and you go away happy and things like that. So of course, our first goal is always to cure people, as many people as we can. And so we provide hope in that sense, that whatever it is we can do to get you to a positive outcome, that's what we want to provide.
Darrin Godin: Thank you. And I know you're seeing patients every day. So tell us about some of the advances and the exciting things that are coming up that really are bringing hope to patients and their families that you're seeing on the horizon.
Dr. Tanya Siddiqi: Yeah. I mean, so as part of my hematology-oncology journey, I realized very early that I have to be involved in research because that is the way to bring newer treatments to patients rather than waiting for somebody else to do the work and get it FDA approved and then being able to provide new treatments to patients. And so at City of Hope, I've always been able to open trials, get new treatments out. And at City of Hope, Orange County where I've been for the last two and a half years and counting, we have brought a number of clinical trials in lymphoma and CLL, which are my specialties. The most exciting stuff that I do and I'm working to bring to Orange County for our patients in Orange County from our main campus, etcetera, are two things.
One is something called CAR T-cell therapy and the other is something called bispecific antibody therapy. And these are newer treatments that are kind of providing a way for us to harness the body's own immune system to fight the cancer rather than subjecting it to poisonous chemotherapy repeatedly and stuff like that, which may work to some extent. But if it doesn't work, then we have to fall back on really other treatments that work equally well and maybe even better. And so one of the big passions of mine is CAR T-cell therapy because I was part of a number of trials at City of Hope that led to FDA approvals in different lymphomas and CLL for this novel treatment option in patients.
Darrin Godin: Tell me more about CAR T-cell therapy. Explain it so that our everyday listener can understand what exactly does that mean? What does it entail and what does it do for our patient?
Dr. Tanya Siddiqi: Sure. So the way I explain it to patients when I'm actually offering them that treatment is I tell them we all have white cells in our bodies to fight infections with, and one of those types of white cells are called lymphocytes. We all have B lymphocytes and T lymphocytes. Most of the diseases I treat, lymphomas, they come from B lymphocytes, meaning one of those B lymphocyte white cells changes into a cancer and that's called a lymphoma. But the T lymphocyte pathway of your immune system is still robust and normal and should be helping fight infections, et cetera. What we do is we take out those T lymphocytes from the blood by a process called apheresis. The blood goes out from one vein, goes through a machine, the machine collects just those immune cells and the patient gets the rest of their blood back. And this process takes about four to six hours to collect a bag of T-cells.
These cells are then sent to the lab depending on whether we're making the T-cells in City of Hope or we're sending them to the company, there are different companies that manufacture CAR T-cells. And so the bag of patient T-cells is sent to the company or wherever, whichever lab will manufacture them. And over there, they use a mechanism of proteins from different viruses, more like HIV-type viruses, but they're not the actual virus, it's just the machinery of the virus that helps make changes in these patient T-cells so that now instead of fighting infections, these cells are trained to lock into the B lymphoma cell cancer cell and target and eat them up or chew them up or whatever, kind of like Pac-Man when you release them back into the body of the patient.
So they now recognize and target the B-cell lymphoma cells. And so this process of manufacturing takes about two to four weeks after which we'll give the patient three days of a certain type of chemo to kind of cut down on how many T lymphocytes the patient has themselves. We give them back their CAR T-cells by the IV infusion. We watch them closely for two weeks afterwards because that's when the main fight is happening between the T-cells and the B-cells. We watch them for hyperinflammation and other side effects. And then we restage them a month after their CAR T-cell infusion. And majority of patients by that time point already have achieved a complete remission. The cancer is gone, the cells have chewed it all up, and after that we just watch the patients over a period of time, make sure the side effects are all gone, and hope that this disease never comes back.
And in aggressive lymphoma, we've cured patients 40, 45% of the time using CAR T-cell therapy by itself, and these are patients who had failed chemo, had failed transplant, were surely going to die, and now they're 40, 45% of them are cured, meaning their disease never came back five years or later. So we're trying to work on that some more and make it even better. There's always room to improve, but already this, I call it... When we were developing it and researching it and actually doing the trials, the way we explain it to patients, it sounds like a lot of science fiction, but it has now become science reality. These are not fiction anymore. This is reality. We are already doing this, this is FDA approved, it's saving lives, and now we're working on next steps, so how are we going to make it even better?
Darrin Godin: It's amazing to think about what is possible and that we can take cells from a person's body and re-engineer them or reprogram them to do that. That's just amazing. So you also talked about bispecific. So can you talk a little bit about what that is and what that means?
Dr. Tanya Siddiqi: Right. So it's a different type of an immunotherapy. So instead of taking out T-cells from a patient's body and manufacturing them into CAR T-cells and going through that whole long and drawn out process, which is very personalized for each patient, but also therefore very resource heavy and financially expensive process and limited to only certain centers across the country who can do these kinds of things, bispecific antibodies are a way of using the patient's own T-cells within the body to kind of draw them towards the cancer so that hey, whatever's already there, can you just start doing your work and chewing up the cancer that's in the body without having to make CAR T-cells. And so it's a little bit cruder way of using T-cells within the body to come join the fight against lymphoma, but it's really... Antibodies have a connection point, so they target it against something.
So one end of that bispecific antibody will go and bind to the lymphoma and try to damage the lymphoma itself, but at the other end, it attaches itself to a T-cell and brings it to the lymphoma. So it brings it closer. And that's how it's asking the T-cells to join the fight against lymphoma. And because it's a cruder way, it's not a one and done infusion like CAR T-cells are. It has to be done on either bi-weekly or a monthly basis depending on which product it is. And it can go on for even a year of therapy this way, if not more, sometimes less depending on which lymphoma it is. But it's also proving to be a good way let's say for patients who can't wait for a month for the CAR T-cells to be manufactured. It's more urgent to treat them faster and things like that. So it's a good option.
Darrin Godin: Are these inpatient or outpatient procedures or are they a little bit of both?
Dr. Tanya Siddiqi: Right. So primarily at City of Hope, we have worked very hard in our main campus to convert all of this to outpatient, so they don't just sit in the hospital for two, three weeks at a time getting their treatments, especially CAR T-cells. Knowing that we have a very good safety net, we watch them closely when we give them the treatment and we'll watch them... We have them stay very close to City of Hope for the first couple days in terms in bispecific antibody terms, but couple of weeks in terms of CAR T-cells and the minute they get a feal first fever, we admit them to the hospital. So that way they don't have to be in the hospital all the time. They can go sleep in their own bed, but they'll come very regularly to the clinic and be monitored very closely in the beginning of their immunotherapy journey.
Darrin Godin: Wow. And how long have we been doing these types of immunotherapies?
Dr. Tanya Siddiqi: So CAR T-cells, I remember the very first trial we were involved with, the first product that was FDA approved for lymphoma was the ZUMA-1 trial with the Kite Pharma's CAR T-cell, what we call now Yescarta or axi-cel. That trial started, I want to say in 2016, and we were one of the only four sites in the country to be part of that study that led to then FDA approval of that. The latest trial that I led at City of Hope was the CLL trial. That's the BMS liso-cel or Breyanzi product, and that was just FDA approved for CLL based on bulk of our work. I want to say a year and a half ago it was... No, it was actually March, 2024. So it's been just a little over a year. And the golden opportunity we now have is to bring all of this to City of Hope, Orange County as our hospital comes to open soon. But even before that, we already have a day hospital where we do outpatient auto-transplants for myeloma and now we're working to start our outpatient CAR T program this summer actually. So we're close.
Darrin Godin: Good time to talk about the hospital since you mentioned it. When the hospital does come online here in Orange County, as you know, it's be Orange County's only specialty hospital 100% focused on treating, researching and curing cancers for patients. What do you think that's going to mean for your patients with blood cancers and other patients that need that inpatient stay? What do you think that's going to mean for them?
Dr. Tanya Siddiqi: Oh, I mean, we are excited. Patients are excited because it really means that the patients who live in Orange County won't have to go all the way to Duarte to receive the special cancer care they might need in the hospital if they have a side effect from transplant or CAR T-cells or chemo or immunotherapy or whatever we do treat them with in the outpatient setting. Or in another situation, they won't need to go to another hospital like one of our neighboring hospitals to seek medical care in the hospital if they have side effects from treatment that we are giving them, right? So we want to be able to just admit them right away, close to ourselves, manage their care directly, make sure they get the best and correct cancer treatments and toxicity management, which is very, very important.
Because if you give somebody CAR T-cells and they go to a local emergency room, the local emergency room docs are not going to know what to do with CAR T side effects because they don't have the experience or knowledge, for instance, just CAR T is the one I'm naming. But there are many other novel treatment options where the smaller community hospitals don't know what they are and how to manage them. So I think for patient care, it's going to be amazing.
Darrin Godin: Awesome. I want to ask you a question. When you talk about being a part of those trials that have gone through FDA approval are now are being used and are becoming more standard of care, if you will, or available, how does that make you feel? I mean, you've impacted a terrible disease that has been having a great impact on people and now you're offering more hope to them. I mean, what does that make you feel like as a researcher, as a scientist?
Dr. Tanya Siddiqi: No, no. I mean it's very fulfilling and satisfying, right? That's why we do the work we do at City of Hope because if it was just a matter of seeing patients, treating patients, you could do that anywhere in the country, right? But to be at a medical center, which keeps research at its forefront, to be on the cutting edge of just bringing novel treatments to patients and actually saving lives, that is truly gratifying. That's what brings us to work every day, essentially. We have so many stories, individual stories of patients who know, who understand, the families understand that they would not have made it years ago if it wasn't for a particular clinical trial and the fact that it worked so well for them and things like that. So they could not have waited until those treatments became FDA approved and commercially available, they would've died before that. So I think it's truly gratifying and just satisfying and we love it.
Darrin Godin: So let's put a finer point on that. When patients come to City of Hope, with the amount of research that we're doing, the amount of clinical trials that we're offering, when there is a clinical trial that they are suited for, they're accessing something that is not available anywhere else. They're accessing something that may not be available for years down the line. So we'd like to say we're bringing tomorrow's cures to patients today.
Dr. Tanya Siddiqi: Absolutely.
Darrin Godin: And that's not marketing speak, right? I mean, that's reality.
Dr. Tanya Siddiqi: That's reality. Yeah.
Darrin Godin: It's amazing. It's amazing.
Dr. Tanya Siddiqi: Yeah, it's amazing. I mean, I will say there a lot of trials we do are open at other sites in the country, but if you live in Orange County, why would you go to Stanford when you can do it at City of Hope in Orange County, right? So it's just the ease of having all these trials available near home is something that wasn't present in Orange County before I can say. So I think it's just a great service to provide.
Darrin Godin: Well, thank you. So as you know, City of Hope is committed to expanding equitable access to its breakthrough research, and you've been accelerating that commitment through the sought after IMPACT Research Grant from the Leukemia and Lymphoma Society. Can you tell us more about that?
Dr. Tanya Siddiqi: Right, so that IMPACT Grant is something that was awarded to me a couple of years ago now from the Leukemia Lymphoma Society. It's a five-year $1.4 million grant, which basically the premise is they want us to use this money to bring hematology trials to the community network sites so that patients who live in more rural areas or away from the big cities or away from our main Duarte campus or the Orange County campuses, which are the biggest campuses for just trial and research and whatnot, they may lose out on these trials if they can't physically make it to these sites. And therefore, if we can open some of the most relevant trials and the most relevant diseases that our clinical network sites see, then those trial options will be available locally in the community to them.
And that's what this grant is providing support for, make sure we have the right personnel in place, the right infrastructure if patients need help or transport to the main campus for certain testing for the study and back home again, hotel stays and whatnot, this provides support for that kind of stuff as well. And so we've opened already 10 or so trials in several communities, network sites that City of Hope owns, and we have like 35 in Southern California, out of which about I want to say seven or eight actually run trials. And so we've opened about 10 hematology trials approximately at these sites. And slowly but surely the physicians there are enrolling onto those studies in multiple myeloma, Hodgkin lymphoma, those kinds of things.
Darrin Godin: What are you seeing right now in terms of how blood cancers are affecting the population? Are you seeing changes in ages or certain ethnic groups or who are you seeing mostly come in and are things changing and you're beginning to notice those shifts?
Dr. Tanya Siddiqi: That's a good question. I think lymphomas in general have been on the rise for the last few decades just in terms of incidence. I think just because as all of us have been exposed more and more to different chemicals, plastics, preservatives, environmental changes, I think over the years, enough DNA damage occurs that sometimes cancer emerges. And lymphoma is one of those types of cancers that comes out of multiple hits from various insults to our DNA, so to speak. And so we know that lymphomas have been on the rise for all these reasons, but I have to admit, I feel like I'm seeing more younger patients with certain lymphomas that were always taught to be afflicting older adults.
We know Hodgkin lymphoma can occur in late teens, early twenties, that's known. But other diseases like CLL, for instance, which is median age for CLL is historically 70 or 72. I have patients in their thirties with CLL now. So when I tell them the same thing that, "Oh, you'll live your whole life. We'll just keep you well and treat when you need treatment." It's a different discussion with a 30-year-old than it is with a 30-year-old, right?
Darrin Godin: Right.
Dr. Tanya Siddiqi: So how am I going to take that 30-year-old to be 90? It may or may not be true when I say that to a 30-year-old, while when I say that to a 70-year-old, 'Hey, you'll live 20 years, no problem unless something else takes you." So that those are the things that I'm noticing, and it's a little bit more of a challenge, and that's why we continue our research to see how can we even cure these historically incurable but slow growing chronic cancers. So because our patients are getting younger and we need to really find the cures for these diseases.
Darrin Godin: And the diseases that you are seeing, how does one usually find out they have that? What are they experiencing? What are some of the symptoms maybe they're having that then... How do they know? I mean, it's a blood sort of thing. How do you know?
Dr. Tanya Siddiqi: Right. So lymphomas are a very heterogeneous kind of a group of diseases. There are 40, 50 different types. And so they can range from very aggressive to very slow growing. So I'll give you an example of either end of the spectrum. So CLL is a very slow growing kind of a B-cell lymphoma. It shows up insidiously, by and large, most people will know nothing about it until they go for the annual physicals. They do a blood test and the doctor says, "Oh, your white count is a little bit elevated. Let's recheck." And they recheck and it's still elevated, and then they get sent to the hematologist, "Something is wrong, the white count is elevated. Can you look into this further?' And we do more testing and we find out, "Oh, it's a very early stage of CLL." And then we watch it wait and intervene when we need to intervene.
The other end of the spectrum is more aggressive lymphoma, something called diffuse large B-cell lymphoma is one of the more common aggressive lymphomas, and most people will notice a lump, "Hey, this lump showed up. Somebody gave me antibiotics. It didn't go away," thinking it was infection related because lymph nodes fight infections. Didn't go away. It keeps growing. Let's go get a biopsy. ENT did a biopsy. They found lymphoma, they get referred to an oncologist. So don't ignore lumps for too long if it doesn't go... Any symptom I say that doesn't go away for a couple of weeks, make sure somebody assesses it and evaluates it further. But most commonly, it's either a lump or it's a blood test that picks things up. Sometimes it's other symptoms like drenching night sweats or weight loss that's unexplained or severe fatigue and things like that. But that usually means more advanced disease. And so to catch it early, don't miss out on some of these other symptoms.
Darrin Godin: Well, along those same lines, what is the message that you have for patients overall, whether it's related directly to blood cancers or others? What is the thing that you tell your friends and your family when it comes to thinking about prevention and what they can do to keep themselves healthy?
Dr. Tanya Siddiqi: That's a hard question in this day and age, because a lot of people turn towards naturopaths and extremes of vitamins and supplements and all that. I usually tell everybody, "You need to have a balanced, healthy diet. Make sure you get enough protein. You still need some carbohydrates. You need to exercise regularly. That's good for the immune system in general. You need to drink plenty of water as opposed to sodas and caffeine and things like that." And you'll get all your vitamins from your food if you have a healthy balance diet, you don't need to take tons of extra vitamins and supplements because the body will just pee it out or shed it out because it doesn't need it. And that just becomes very expensive urine then, as one of my mentors used to say. But just common sense stuff.
I think even people ask me when they first get diagnosed with cancer, "I stopped eating sugar because we heard sugar feeds cancer." And I always say, "That's in the Petri dish." We know that cancers have glucose receptors and therefore take up glucose to grow, but the body always makes glucose because our brain and our heart cannot live without glucose. So you'll never get glucose out of your system because you can't survive without it. So then just be smart and don't have all the cakes and donuts. Just have fresh fruits and smarter sugar containing foods. You don't have to give up... You don't have to be that extreme. So balanced, healthy stuff, I am okay with. You're not going to harm yourself.
Darrin Godin: All right. Well, thank you so much and we really appreciate you taking the time today to talk to us and walk us through some of these things and explaining them in such a way that we can understand and we're grateful for the work that you're doing and the impact you're having on our patients and our community. And the exciting thing to me is every time I talk to one of our doctors like you, I think there's more than 600 of you at City of Hope and there's 1,000 researchers that are behind you in labs that are-
Dr. Tanya Siddiqi: That's true.
Darrin Godin: Doing the things every single day to help advance the work that is so important for you and for our patients. So it's really a special place and we're grateful for it. But thank you for your time.
Dr. Tanya Siddiqi: Yeah. It's a lot of team effort. You're right. But thank you for getting the word out. I think that's important.
Darrin Godin: Well, what a great conversation with Dr. Tanya Siddiqi. She and the work she is doing along with all of our team is really the reason why City of Hope is top five ranked cancer care in the nation. And it's available right here in Orange County. If you or a loved one need more information, please visit us at cityofhope.org/oc or call us at (877) 541-4673. I'm Darrin Godin. Thank you so much for listening to Talking Hope, and we look forward to our next discussion with you next time.