Episode 3: CAR T-Cell Therapy: Engineering the Immune System to Fight Cancer with Dr. Gary Simmons
Intro: (music overlay)
Welcome to Cancer Care Connections. On this week's episode, Cheryl Tan spoke with Dr. Gary Simmons. Dr. Simmons is a hematologist oncologist and part of the transplant and cellular therapy team for Virginia Oncology Associates. Cheryl and Dr. Simmons dove into CAR T-cell therapy, how it is a revolutionary treatment for fighting blood cancer, and how continued research of CAR T could change the landscape of cancer treatment.
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Cheryl
Our guest today is Dr. Gary Simmons, who joined Virginia Oncology Associates in 2023. He's a leader in CAR T-cell therapy, performing research, publishing papers, and giving local, regional, and national talks. He has seen the transformational opportunity of cellular therapy and is passionate about access to this therapy for all who need it. In his spare time...Not sure how much he has, [laughter] he enjoys being a father to his five kids and running ultramarathons. He has completed several 100-mile endurance runs and once ran 100 miles on a treadmill. I'm looking at you right now. I thought I was a runner, but I think you definitely take the cake, Dr. Simmons.
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Dr. Gary Simmons
Well, I think having five kids will force you to run very far, to be frank.
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Cheryl
I agree. I agree. I have three kids. I don't have five. I have three. But that's why I like to run.
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Dr. Simmons
It's good. They're good challenges. They're definitely good challenges.
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Cheryl
How did you get started with that?
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Dr. Simmons
With ultramarathons?
Cheryl
Yeah.
Dr. Simmons
Um, I started with ultramarathon running, probably through...I started out doing marathons in medical school, and then my buddy and I, who's now an orthopedic surgeon, really just sort of started running a little farther back in Maine in 2007, I think it was. And we ran a 44-mile run for global health, and we raised money for that.
00;02;07;21 - 00;02;14;28
Dr. Simmons
And that went into a 50-mile run the next year. And you just kept going up. So that's how it really started.
00;02;14;29 - 00;02;19;04
Cheryl
It's like trying to better yourself and you're helping a cause as well.
00;02;19;09 - 00;03;23;12
Dr. Simmons
That that too. But you know what's interesting about Ultramarathons, specifically 100-mile races, it's very complicated. We don't have the time to delve into why we do these sorts of things. But I will say what I like about it is that it's life in a day because there are lots of highs, there are lots of lows, and the majority of time is just kind of intermediate, you know, and it's kind of like trying to figure out how to navigate, ride the highs, get through the lows, and plunge through the sort of boring intermediate times.
And it's really like a patient with like a journey through cancer, right? With patients, there are some highs when you get good results or some lows when you get bad results. A lot of days it's just labs and treatments and things like that. And I think honestly, that parallel attracted me more and more as I started my career out in stem cell transplants and sort of seeing patients go through long, you know, treatment journeys and stuff like that.
And I don't know, I think it just kind of all kind of came together for me that way.
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Cheryl
I can see that as you're describing that, I can see it in my head how a patient's journey is really an up and down and you put your body through that in your marathon running as kind of a way to sort of understand that a little.
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Dr. Simmons
Yeah, in a sense, yeah. In a sense. You know, I'm definitely not trying to put myself in their shoes, but I think there was definitely some sort of parallel to that, you know? And I can feel that.
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Cheryl
I know you're passionate as well about cellular therapy, about CAR-T cell therapy. And I want to really talk about that and how this became another one of your passions.
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Dr. Simmons
Yeah, well, I mean, I think timing is, you know, they say timing is everything, right? And I think I was really blessed with my timing in my sort of career and my opportunity at VCU. You know, I did my training at VCU and I really learned a lot from the program there. And in the doctors there. And I and I have a lot of gratitude for that place.
And at VCU, really is where CAR T-cells started coming out in 2016, 2017, right when I was starting my career. And I was just kind of ready to dive into it. And the doctors that I was working with were ready to take it all on. And really at the time, you know, we were doing these high-intensity transplants for lymphomas and you know, it would require patients to travel to Richmond and take on six months of therapy and being away from their family for six months for cure abilities that were about 50% and come with toxicities.
And then we'd have these CAR T-cells that we could give them that were sort of for the same lymphomas, and we could do it in about two weeks and we could have similar amazing results without the toxicities. And it really just sort of opened my eyes to the possibility of what cell therapy could bring with less toxicity, less burden to the patient and their families, and super great results.
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Cheryl
I can see how you can get behind that. That's for sure. Let's go back a little bit. Can we just define and explain what cell therapy is? In particular, what are car T-cells?
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Dr. Simmons
Yeah, good question. So in cancer care, there's really, you know, a few different modalities to treat it. You can cut it out or shoot radiation at it. You know, that's surgery and radiation. And then in the medical oncology field, there are drug therapies. And now more specifically, we recognize and I think the doctors that have come before me have known for a while how powerful the immune system is at killing cancer because cancer is very smart.
It has certain mutations in the cells to sort of prevent itself from dying against your drug. But the immune system is very smart as well, and it overcomes those mutations. And so what allogeneic transplants are, are replacing the immune systems. And we've known for a long time in blood cancers that that's very successful at killing off and eradicating cancer forever.
It just comes at a high cost. And that's what I was talking about, that long journey. So cellular therapy or more specifically car T-cell therapies are taking the patient's T-cells out and genetically modifying them or engineering them to kill the cancer and then giving them back. So it's the patient's own T-cells, which is much safer for them.
And secondly, it's sort of teaching the T-cell that might be sort of sleepy at the wheel, if you will, to find the cancer cell and get rid of it.
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Cheryl
I'm just processing that. So everyone has that ability. Everyone has a T-cell that can be modified and made better, in a sense.
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Dr. Simmons
Correct. Yeah. I mean, I think yes, the answer is yes. I think what's exciting to me is that you know, this is all very novel and new to me and I'm new to the field right now. We use the patient's own T-cells. Yes, we all have T-cells that can be modified and engineered.
However, I think the science started pointing to using healthier T-cells, younger T-cells, maybe from somebody else that are sort of engineered differently and ready to go. Because in the CAR T-cell world, if you're using your own T-cells, it has to be taken out of your body. That's a process that takes a few hours and then the cells have to be shipped away and manufactured and engineered, which takes another 2 to 3 weeks. And all that time is, you know, adds up for the patient waiting for the therapy.
And if there is an alternative method like the car T-cells are sort of already engineered and sitting there waiting for you, you save about a month of therapy, but yeah, it's we all have this possibility. I think the future is going to point towards potentially having these cells already available for us and for the patients.
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Cheryl
That's so interesting. So kind of like you're going to the store and..the T-cell store, you will pull something off the shelf that is matching whatever you might need it for. And so that leads to my next question, what needs can be met? What diseases can the car-T cells treat?
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Dr. Simmons
Yeah, good question. So right now the current FDA-approved CAR T-cell therapies will treat diseases such as myeloma, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, or ALL. Those are some of the big ones. These are the B-cell blood cancers if you will. Okay. So those are where the FDA products are sort of already available to us and to the patients.
Other things would be through clinical trials. Now, the one limitation I will bring up as we talk about CAR T-cells and if I was a patient with any sort of cancer, I would be asking the doctor, "Well, why can't I have this for my cancer?" And I think that's a great question. The limitation to CAR T-cells is that CAR T-cells can only sort of kill what it sees.
Okay, So 25% of cancer proteins are on the outside of the cell, which makes a good target for a CAR T-cell. But 75% of cancer proteins are inside the cell and CAR T-cells can't help in that respect. And there are lots of cancers like leukemias and some others where a lot of the problem is internal. All in the CAR is not helpful.
So many people ask me, are there CAR T-cells for this cancer? And sometimes the answer is no because there's just not a good target for it. That's number one. And number two, the other limitation to CAR T-cells is that the CAR does kill what it sees. So if there is a cancer protein that is expressed on healthy tissue and cancer tissue, the CAR T-cell kills it no matter what.
So we have to be careful of what the CAR can do because if you start hurting normal tissue, lung tissue, heart tissue, there's a limitation. So sometimes people ask me, is there a CAR for this cancer? And there is. But it also would knock out your lung tissue as well and you can't breathe. So there are limitations to what T-cell technologies can do, specifically the CAR.
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Cheryl
So it's highly, highly effective but not highly appropriate for every single illness.
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Dr. Simmons
Correct.
00;11;04;01 - 00;11;33;23
Cheryl
And I know we talked about blood cancers in a recent episode with Dr. Jared Kobulnicky, and I appreciate the opportunity to go deeper into CAR T-cell therapy so we can do that here. So again, just thank you for this opportunity to learn about something that you're so passionate about and is growing in interest. I'm sure you get many opportunities to speak about this.
I know you speak nationally, and regionally about this topic. How did that come about?
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Dr. Simmons
Really just in a way of putting yourself out there. I kind of, when I first started out, I really wanted to help. I guess is probably the best way to describe it. And I think I think there's a lot of information online for folks, and I think that it's great, it's great for transparency, it's great for patients and their families to have access.
But I also think it's important to kind of get it from the horse's mouth. And back at VCU and in Richmond, I would give support talks or, you know, give talks to support groups for myeloma, lymphoma. And I still always put myself out there in that respect in Virginia Beach now as well. And again, the message is really just to give accurate information about what CAR T-cells are, or cell therapy in general, or stem cell transplant, because these therapies have the potential to be very, very powerful in treating the disease and even curative.
And if there are one or two people out there that just hear that, I'm happy to help them..or if there are people out there that are looking online and are too scared to even come in and talk about it, if we can impact one or two of them, that's helpful too. So I try to...
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Cheryl
I think people appreciate, they appreciate hearing that message, you know, that somebody is interested in explaining and helping them understand what this could mean. So I'd love to hear about how you've used CAR T in your practice. Have you used this, would you call it technology, this information to help your patients get better?
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Dr. Simmons
Yeah. So I think in my experience we've been developing programs. This is novel therapy in cancer care. Things start out in clinical trials. We've got to prove that they're safe and efficacious and they've got to go through a rigorous process and then be FDA-approved. And so once cancer treatments like CAR T-cells are FDA approved, then programs have to be built.
There are lots of regulations, there are lots of moving parts that have to be able to be in place so that the infrastructure is available to give the product safely. And so a lot of my career and what I really enjoy doing is building programs. As you build programs, you open up access to patients. And so I started in Richmond, in Virginia at VCU, and now I'm grateful to be at VOA and building a program here.
So we've got a lot of good experience using the CAR T-cells in different blood cancers and in clinical trials. And at this point, what I'm trying to do is open up more access to patients in this area for them in the future.
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Cheryl
What does that mean for patients here at Virginia Oncology Associates? Is this a place they go to get that therapy, to get, clearly answers from someone like you or someone in your office? But what does this mean for a patient here?
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Dr. Simmons
Yeah, this is...I'm hoping that this will be great for patients here now, and more importantly in the future, as we build our program and bring on more CAR T-cell and gene therapies as well as clinical trials. But what this means for the patients here and their families is that if they're seeing us or if they have a cancer that is... there's a clinical trial or there's a...or we have the car T-cell product available for their myeloma or lymphoma, that they can come here and they can stay here.
They don't have to go to Richmond and relocate their family. They don't have to go to Duke. Both are wonderful places, but if you can stay in your own bed, eat your own food at home and come and get your CAR T-cells where you live, I think that opens up the opportunity for more access to patients.
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Cheryl
Can you give me an idea of what that looks like? Maybe you have a patient in mind who has found success with this and kind of what they're their process was, as you mentioned, being able to go home and eat their own food. Is that really possible? And how long did that take...the whole thing?
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Dr. Simmons
Yeah. Yeah. I mean, I think as science evolves and technology evolves and we get better at doing this, we recognize that we can do some, most, not all, outpatient. So some of these things we do in the outpatient setting. So, you know, here we're, we're building our program and using the infrastructure that the group has developed over the years prior to me coming here and really allowing the patients to come in, get the chemotherapies before we do the CAR T-cells (which is the standard of care), and then we give them the CAR T-cells in the clinic here. And then we have a process of monitoring them after we give the CAR T-cells, but allowing them to be home, keeping a journal. We're always on call, we always have check-ins and we see them pretty much every day after the CAR T-cells in the clinic. So if they live locally or 30 to 40 minutes away, their caregiver can drive them home. They come back the next day. If there's an issue at night or fever at night or any issue that we're called about at night and we kind of handle it that way, but you know we try to keep them home and safe.
We know that does a lot spiritually, mentally, and, you know, there's a lot of good involved in sort of keeping them home. But more importantly, it's keeping them local because I've met so many patients that do not have the capability to leave their home, whether they're a single mother with a few kids at home or they just don't have the caregiver needs or whatever.
So we're really trying to build the programs, and I hope this is happening throughout the country, and I'm sure it is. But build these programs so that more people get access because that's the keyword.
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Cheryl
Well, as you're explaining to me what that involves, that's why when you said earlier people would move to the cities where those treatment centers are available, they need to you need to have access on a daily basis to this kind of medical care, medical treatment, medical oversight. And so having something like this in Hampton Roads is critical for the people in our area.
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Dr. Simmons
Exactly.
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Cheryl
Does a patient need to be in a hospital setting to receive this CAR T-cell therapy?
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Dr. Simmons
The answer is no. They don't need to be in the hospital setting. It's been my experience that in terms of the CAR T-cell process, from the time you are really in it, you get some chemotherapy for a few days, which is very gentle chemotherapy, and then you get your CAR T-cell infusion and then you're really supposed to be monitored very safely for about seven days or so thereafter.
So if you add those days up, it's about two weeks. Okay. In that two-week period, there are several patients who can stay out of the hospital the entire time. So they do not need to be in the hospital. Now, I also don't want to minimize some of the side effects of this. And they do require the right infrastructure in management and oversight.
And so in my experience, I still argue three out of...3 to 4 out of ten people or 30% or so do end up in a hospital at some point. Now it might just be for a day or two. It might be for a longer period of time. But it's been my experience that about 30 to 40% still end up in the hospital, but they don't need to be there unless they need to be there.
And there are still seven or so out of ten that can stay out of the hospital.
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Cheryl
And have the outpatient care that you mentioned earlier.
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Dr. Simmons
Exactly.
00;19;06;17 - 00;19;29;01
Cheryl
You were talking earlier about wanting to be the guidance. If people have questions and I imagine you get quite a few questions or more and more questions as this advancement comes to light more. Are there misconceptions you'd like to address, things that you'd like them or us to know about that you get asked about all the time?
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Dr. Simmons
Yeah, I think that's a really good question, one that I haven't been asked before. I think that patients should seek out wherever they're closest to their authorized treatment centers. There are authorized treatment centers that can give CAR T-cells, and I think it would be important to discuss with those doctors that actually perform the procedure and experience doing it before they sort of make these preconceived decisions.
So in general, CAR T-cells are probably a little bit safer now than they were. And again, we have to trust the science. The science has gotten us this far and it continues to evolve. For example, when I first started CAR T-cells with our group at VCU, we did about..in the beginning, we would have everybody in the hospital, we would check their bloodwork 2 to 3 times a day, and it was very rigorous and all of us across the country were doing things similarly. Now...It's much more evolved. We do them outpatient. You know, people are going home at night. So just in a few years...six, seven years or so, there's been tremendous evolution. If something was so toxic and serious, we would never allow that to occur. So I think there's a lot of...I think it's best to just talk to the authorized treatment centers; the doctors who are performing the procedures, because there are a lot of variabilities that are hard to extrapolate either in person or on paper.
And what that means is somebody with a lot of cancer cells may be more prone to having more reactions than somebody with very little cancer cells. So the patients reading these things online, maybe not be understanding, maybe, maybe not know all that. And that's why it's really important to talk to the docs, because I can look at some people and say, "We could have some toxicities here. And this is what I kind of expect from the data as well as my experience" versus someone I may say, "I think you'll do very well outpatient with minimal toxicities."
00;21;24;23 - 00;21;44;09
Cheryl
Everyone's different.
Dr. Simmons
Everyone's different.
Cheryl
Everyone deals with this differently as well. What does the future hold for CAR T-cell therapy? I mean, you mentioned just now how in the last few years things have changed in the way you treat patients...just outpatient, inpatient. What do you think is kind of the future for it?
00;21;44;11 - 00;23;37;12
Dr. Simmons
Well, I think the future of oncology is cellular therapy. And I think CAR T-cells have great potential in the space that they're in, with the ability to become sort of off the shelf, where we can just pull them and give them and not have to go through the manufacturing space. I think cellular therapy with T-cells has a huge potential in the future to treat solid tumors, breast cancers, lung cancers, ovarian cancers, and things like that.
So I think there's going to be a lot of trials coming out. There already are a lot of trials and we will hopefully have a lot of these trials here. But the future is going to be really big in my career with T-cell therapies; drugs giving...that are called BITES bispecific molecules, which are drugs that bring the T-cell and the cancer cell together.
Again, all this is on the backbone of T-cells. And I think that's the driving force in really trying to eradicate cancer. And secondly, I would say that cellular therapy is really picking up too, with gene therapy. Okay. So what that means is sort of taking cells out of the body like a CAR. What we do in car T-cells is we take the T-cell out and we engineer it to fight cancer.
But what if you take the stem cell out and put in a gene that makes blood? Well, that helps with sickle cell, that has the potential to cure sickle cell disease or thalassemia or hemophilia. Okay. So all these genetic disorders that are sort of one gene mutated, and there are lots of data and trials that are supporting this. And I think that's very exciting.
So it works off the backbone of that cellular therapy, CAR T-cell technology, but in a different format.
00;23;37;14 - 00;23;52;12
Cheryl
Very exciting. Very, very exciting. We've got a lot of work to do, huh? What is the message, for people listening who maybe it's a patient, maybe it's a family member of a patient? How do they use this information?
00;23;52;14 - 00;24;42;10
Dr. Simmons
Yeah, that's a good question. I think the message I would give to them would be to seek out your care, you know, find treatment centers that offer these sorts of therapies. They're already out there. There are a lot of them out there. I would ask people to not only search in the large academic centers because I think places like VOA and some other programs are super and have super docs and super technology and super clinical trials that will help them and they may be driving right past them to go somewhere else.
So as you look online, I think it's important to recognize that there are lots of programs that offer these cellular therapies. But I think I think it's important to sort of seek it all out.
00;24;42;13 - 00;24;43;04
Cheryl
Do your homework.
00;24;43;07 - 00;24;44;17
Speaker 3
Do your homework.
00;24;44;19 - 00;24;53;28
Cheryl
Do your homework. Thank you so much for your time. It's been a pleasure talking to you and hearing all about this technology and what you think is ahead. Thanks, Doctor Simmons.
00;24;53;28 - 00;24;56;10
Dr. Simmons
Thank you. Thank you for your time.
00;24;56;12 - 00;25;57;25
Exit- (music overlay)
That’s all for this episode of Cancer Care Connections. Stay tuned for our next episode where Cheryl will be talking with Tifany Lewis, the Manager of Genetic Counseling for Virginia Oncology Associates. They will break down how genetic testing with VOA differs from direct-to-consumer genetic testing you can purchase online as well as the role genetic counselors play in your genetic testing journey.
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