Understanding CAR T Therapy Transcript
Voiceover: CAR T therapy is an innovative and groundbreaking approach in the treatment of multiple myeloma.
Dr. Brian G.M. Durie: This type of therapy has been described as a game-changer.
Donna Catamero: It's a very personalized, directed approach in the treatment of myeloma.
Dr. Joseph Mikhael: We can very specifically use someone's own immune system to destroy their own tumor.
Thomas Belfort: What the CAR T has given me truly is a new lease on life.
Voiceover: Eight years ago, Tom Belfort was diagnosed with multiple myeloma.
Thomas Belfort: I had never heard of multiple myeloma. It was just not part of my vocabulary.
Voiceover: Multiple myeloma is a blood cancer that affects the bone marrow. More than 160,000 Americans are currently diagnosed with this disease.
Dr. Joseph Mikhael: We call it a blood cancer because the cell that is cancerous begins in the bone marrow, which is the factory of our blood. It's a special cell called a plasma cell. They grow within the bone marrow and sometimes, they actually escape the bone marrow and can collect in other places, forming little, if you will, micro tumors throughout the body.
Voiceover: Tom was 68 years old when he was diagnosed with myeloma and had just retired from a successful career as a sound supervisor on theatrical films.
Thomas Belfort: It was a complete shock. Just trying to wrap my mind around what exactly does this mean and what are the implications for my life?
Voiceover: Not only had Tom led an active professional life, but he and his wife Victoria loved raising their two children.
Thomas Belfort: How to balance my work life with my family life was always somewhat of a struggle. Being a sound supervisor, you work on a fairly rigid schedule. You are not in charge of your daily life, the production is.
Voiceover: In retirement, they were looking forward to spending more time with their grandchildren and traveling.
Thomas Belfort: The exciting part of being retired is all the freedom that it brings to you. You're no longer tethered to an office, to any schedule but your own.
Voiceover: But six months after Tom retired, he began experiencing chest pains. Scans revealed lesions on his sternum. In August of 2013, Tom began his first treatment for myeloma.
Thomas Belfort: It's a real struggle to not become the disease, to not let the disease conquer you either physically or emotionally.
Voiceover: Over the course of eight years, Tom had a number of different treatments for his multiple myeloma — some harder and much more time-consuming than others.
Thomas Belfort: I started these long infusions. It was a constant reminder of having the disease. Being tethered to the hospital for six-ish hours per infusion.
Victoria de Mara: His initial treatments required him to be around for three weeks out of the month.
Thomas Belfort: So, those were really long days, and it restricted my movements. I couldn't go anywhere really to travel.
Voiceover: By the winter of 2019, the myeloma returned, and Tom's doctors suggested he enter a clinical trial for CAR T therapy.
Thomas Belfort: It was real clear that I did not have that many options available at that time, and that's when they proposed this other clinical trial called CAR T. I'd never heard of it. I didn't know what it was. So, we spent quite a bit of time discussing exactly what it meant and what the procedures would be.
Voiceover: Tom and his wife also found great insight about the treatment, not just from his doctors but also from patients they met through their local IMF support group.
Thomas Belfort: I was aware that there were two women in that group that had had the CAR T-cell therapy a year before I did. And so, I did not go into the clinical trial blind. I was aware of what the pitfalls, the side effects would be and that was a great source of comfort.
Voiceover: CAR T-cell therapy is a type of cancer immunotherapy that can find and fight cancer.
Dr. Joseph Mikhael: We have these T cells in our body that are part of our white cell system that are kind of like the soldiers and the defenders of our body that are trained to be able to fight. We put literally a receptor on the T cell, it's called a chimeric antigen receptor, and the T cells now train to recognize the tumor, will go and find that tumor and help destroy it. We can very specifically use someone's own immune system to destroy their own tumor.
Voiceover: The T cell with the CAR, which stands for chimeric antigen receptor, helps find and fight specific, targeted cells which includes cancer and healthy cells.
Dr. Brian G.M. Durie: This is a rather clever genetic engineering approach to allow the creation of these targeted T cells.
Voiceover: The first step in the CAR T therapy process is to have a patient's blood collected and T cells removed. This is called apheresis.
Donna Catamero: The process of collecting T cells is very similar to the process when patients undergo a stem cell transplant and how we collect the stem cells. So, patients are placed on a machine that looks very similar to a dialysis machine. It pulls out the T cells. It's a one-day procedure, typically three to four hours.
Thomas Belfort: The apheresis is not painful at all. Having the apheresis is somewhat akin to having your blood drawn.
Donna Catamero: The blood goes through the machine, and it pulls out the T cells; it returns the remaining blood to the patient.
Voiceover: After the T cells are collected, they are sent to a manufacturing facility where the CARs or chimeric antigen receptors are added.
Donna Catamero: It takes about four to six weeks for the cells to be manufactured and during that time, we may opt to give the patient bridging chemotherapy.
Dr. Brian G.M. Durie: Many of these patients have active myeloma and they can't really be off treatment for any length of time.
Voiceover: A few days before CAR T-cell therapy, the patient receives low-dose chemotherapy to help their body prepare for the treatment.
Donna Catamero: Once the cells are ready, they will come in and receive an additional chemotherapy called lymphodepleting chemotherapy.
Dr. Brian G.M. Durie: You use a combination of drugs to lymphodeplete, so then to prepare the body to accept this big dose of the engineered T cells.
Voiceover: The one-time infusion of the CAR T cells takes place in a hospital; it is an inpatient procedure.
Thomas Belfort: The newly re-engineered blood is introduced into your body and that's just a regular infusion there is no pain associated with that process whatsoever.
Voiceover: Even though the infusion itself is not painful, there can be significant and serious side effects. Patients stay in the hospital for at least seven days to be monitored for any complications.
Dr. Joseph Mikhael: One of the most worrisome side effects that we've seen with CAR T-cell therapy, it's called cytokine release syndrome and it's really a function of the immune system's response to this reinfusion of T cells that come back into the body, where patients can experience sometimes, something as simple as a little bit of fever and feel slightly unwell. But in some situations, it can really affect people's thinking and can require people to go into the Intensive Care Unit.
Dr. Brian G.M. Durie: CAR T therapy wipes out the myeloma cells rather quickly, sort of like an explosion and so then all of the debris from the destroyed cells are released into the system. And this can be a release of toxins, which can really create a number of problems.
Voiceover: This cytokine storm can cause other side effects including fever, chills, shaking chills, fast or irregular heartbeat, drop in blood pressure, lightheadedness or dizziness, shortness of breath, headache, nausea, fatigue, confusion, swelling, stomach pain.
Donna Catamero: Another unique side effect is something we call neurotoxicity, where patients might feel lethargic, confused, difficulty swallowing, and again that's the reason we keep the patients in the hospital so that we can manage these side effects.
Voiceover: Like many patients, Tom experienced side effects after the CAR T cell infusion.
Thomas Belfort: What I remember is for two days I had fevers that that were, you know, around 103, so fairly high, shivers some amount of pain. But I was aware also that this was very temporary. Maybe a day or two afterwards, I was absolutely back to normal.
Donna Catamero: Patients often worry about the side effects of CAR T therapy. Although side effects can potentially be serious, they are very manageable and treatable.
Voiceover: Patients can leave the hospital once their health care team determines it's safe.
Donna Catamero: We will monitor the patient very closely. But these side effects can occur from the time to infusion to 30 days post-infusion, so even though the patient is discharged, they do need a caregiver, in case they do have prolonged side effects.
Voiceover: Despite the potential for serious and life-threatening side effects, there are critical and key benefits to CAR T therapy.
Dr. Brian G.M. Durie: One of the fantastic things about this therapy is that it is a single therapy.
Donna Catamero: Maintenance therapy is not required with CAR T therapy. This is absolutely groundbreaking for the treatment of myeloma.
Voiceover: For Tom, the benefits of a one-time therapy outweighed any risks.
Thomas Belfort: I was aware that it was a one-time treatment. Once you were done with the treatment, once you're out of the hospital, you could lead a perfectly normal, healthy life no longer tethered to a hospital.
Voiceover: That freedom has finally allowed Tom and his wife to enjoy his retirement.
Thomas Belfort: After CAR T, you just resume the life you always had. I am not tired. I am pain-free. I am lesion-free. I do my labs once a month, but short of that, I do what I want to do when I want to do it.
Victoria de Mara: I would recommend this therapy for anybody. It's a life-changer. It just frees you up to do whatever you want.
Dr. Brian G.M. Durie: For many patients, this is the first time that they have been treatment-free often for many years.
Voiceover: And CAR T therapy has had a dramatic impact on the course of Tom's disease.
Thomas Belfort: It's the first time in the journey of my disease that I have achieved complete remission, what's called MRD negative. I had never been able to achieve that before.
Voiceover: Recent studies on CAR T therapy have shown promising results for a number of patients.
Dr. Brian G.M. Durie: The KarMMa trial was reported in the prestigious New England Journal of Medicine. This was a phase two trial which incorporated 140 patients, of which 128 actually received the engineered T cells. Of those patients, what was extremely positive and encouraging is that 73 percent of the patients responded to treatment and of those, there was a 33 percent, out of the total, actually had what we would call a complete remission and 26 percent actually achieved what we call minimal residual disease. So, what you do is you check a hundred thousand cells and see if any of them in the bone marrow are myeloma and if that is zero then this is called MRD negative at ten to the minus five. And so, 26 percent of the patients did achieve this indication of really excellent response.
Dr. Joseph Mikhael: We're seeing response rates that we've never seen before in heavily pre-treated myeloma over 70 percent, we're seeing people stay in remission for a year or greater on this kind of therapy.
Dr. Brian G.M. Durie: There is a tremendous excitement for patients, and I think that the idea that there can be a prolonged remission without therapy is very attractive.
Voiceover: Based on the success of the KarMMa trial, CAR T therapy is currently approved for patients who have received at least four lines of prior therapy.
Dr. Brian G.M. Durie: These are patients with a quite advanced disease that had relapsed several times and so they are in desperate need of some alternate therapy to work well and try to achieve a remission. And so, there's a lot of optimism that these patients with very advanced disease are having this amazing response.
Dr. Joseph Mikhael: We do anticipate that we'll be able to use CAR T-cell therapy earlier in the disease course.
Donna Catamero: Essentially, they're getting their life back. Their quality of life is back before they were diagnosed with multiple myeloma.
Voiceover: That's the case for Tom and his wife Victoria. CAR T therapy has helped give them back the life they once led.
Thomas Belfort: What the CAR T has given me, truly, is a new lease on life — the ability to travel again, the ability to see friends again. I am leading a perfectly healthy normal life without any side effects. It's profound and liberating because you are not reminded on a daily basis that you have cancer.
Victoria de Mara: We live each day enjoying it to the fullest and not hampered by the mechanics of cancer cure or cancer treatment.
Thomas Belfort: And part of not becoming the disease is not having to think every day about the disease. And that's a very powerful tool.
