Late Effects and Quality of Life after CAR T-cell Therapy

Transcript

(00:00:00) [Susan Stewart] Speaker Introduction. Hello and welcome to the workshop, Late Effects and Quality of Life After CAR T-cell Therapy. My name is Susan Stewart and it's my pleasure to introduce today's speaker Dr. Connor Johnson.

Dr. Johnson is an assistant professor of medicine at Harvard Medical School and an attending oncologist at Massachusetts General Hospital. He specializes in cellular therapy such as CAR T-cell therapy and the treatment of patients with lymphoma. Dr. Johnson's research focuses on addressing the supportive care needs and mitigating the therapy-related toxicity of patients with lymphoma, those receiving cellular therapy and lymphoma survivors. Please join me in welcoming Dr. Johnson.

(00:00:50) [Dr. Connor Johnson]Thank you so much. I'm delighted to be here today and I think this is such an important topic. I hope that today's discussion, both the presentation and our Q&A, is both informative and helpful for all of you. I'd like to move straight into a couple of our slides that summarize the terrific introduction and then right into our outline for today.

(00:01:15) So, we're going to begin with an overview about CAR T-cells. I'm going to focus on the journey that patients experience during CAR T-cells and then we're going to turn our attention to the psychosocial experience, the lived experience of patients and their caregivers and family members going through CAR T-cells. And then we'll spend a good amount of time focusing on the early recovery and long-term effects for those going through CAR T-cell therapy as well as survivorship. So without further ado, let's dive in.

(00:01:51) CAR T-cell therapy stands for Chimeric Antigen Receptor T-cell therapy and, as a treatment, this really is a specialized immunotherapy. Meaning that as opposed to say chemotherapy, which is medications that essentially kill cells directly, we use this treatment as a way of taking the own body's immune system and treating cancer via that.

(00:02:19) We've gone from no approved CAR T-cell therapies in 2016 to six fully FDA-approved products in a very short period of time. Those products are approved to treat blood cancers: some types of lymphoma, leukemia and multiple myeloma. There are hundreds of clinical trials ongoing both at our center and many, many other centers looking at this type of therapy in other blood cancers and in solid tumor malignancies.

(00:02:54) This is a slide that summarizes what a CAR T-cell there is. We take a normal T-cell, which has broad functions to fight infections but also abnormal cells in the body, and we build in a latch, or protein binding area, that will target the cancer cell. That's represented by these two little rectangles at the top. That latch allows the immune system to better see the cancer. The cancer is able to hide from the body naturally because it's an altered version of ourselves. So really, what this is, a genetically engineered or altered T-cell that targets the cancer.

(00:03:41) CAR T-cells are complicated compared to what we think about for a typical drug. For a typical drug, we prescribe it, we schedule a date to give it ,and we start. But because CAR T-cells come from the person's own body, these are autologous T-cells - they're from the patient, the first step is to collect the patient’s T-cells. This is typically a scheduled session where a person has a special catheter or IV in the arm or the neck, and then a machine filters out the T-cells over a three to four-hour period.

Then, those CAR T-cells have to be manufactured or created. Remember, they have to be genetically engineered to express that special latch, and that typically takes anywhere from 17 days to 30 days, depending upon which CAR T-cell is being used. The company making the CAR T-cell will ensure that the CAR T-cells are alive and that they expand to the right number of CAR T-cells for the treatment. They also make sure that they have the proper characteristics to be used. They're then sent back to the treating center.

If I'm treating a patient at Mass General, we will give a short course of chemotherapy - usually two or three days - to make space for the CAR T-cells to grow. Then the CAR T-cells are given as a single infusion, either inpatient or outpatient. These steps are multifaceted and take time, which is a little bit different than prescribing a pill or an infusion.

(00:05:26) Cancers for which there are FDA-approved CAR T products. A little bit of information about what cancers have approvals in 2024 for CAR T-cells. As I mentioned, it's blood cancers right now:  certain types of lymphomas, including aggressive or fast-growing lymphomas where CAR T-cells can be used after one or two other prior treatments. Also, some low-grade lymphomas, which are also called indolent lymphomas, such as follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia which is also considered a low-grade lymphoma or low-grade leukemia.

In addition to these, there is a type of aggressive leukemia called acute lymphoblastic leukemia (ALL), that CAR T-cells are approved for, as well as multiple myeloma. Usually for these diseases, CAR T-cells are approved after multiple lines of therapy. There's been some recent approval moving up CAR T-cells in multiple myeloma in certain situations to as early as the second line of therapy.

(00:06:26) Now let's talk about the patient journey. I referenced some of this on the prior slide, but I think this is very, very important.

Up at the top, the first step of CAR T-cell therapy, once the decision has been made to proceed, is to collect those T-cells from the patient. And that's a procedure referred to as leukapheresis, which looks a lot like donating blood.

Then it takes time to make the CAR T-cells. So sometimes we will give treatment referred to as bridging therapy - building a bridge to the CAR T-cells - to control the cancer while we wait for the CAR T-cells to be created and manufactured properly.

When it comes time to give CAR T-cells, we give two or three days of chemotherapy to lower the blood counts and allow the CAR T-cells to grow properly. And then patients either receive the CAR T-cells in the outpatient setting, meaning in clinic where you're seen frequently, or in the hospital. When people are in the hospital, they're typically hospitalized for seven to 14 days.

We then monitor patients very carefully in the first month after CAR T-cells, mostly for specific toxicities that we're going to talk more about on some subsequent slides.

After 30 days, that's when we typically assess the patient’s response to the CAR T-cells. We continue to assess that over time, but that's typically the first time that we're looking at their response based on scans, blood work, and physical exams.In the long-term, we keep out an eye for rare side effects that can be long-term side effects of CAR T-cells.

(00:08:04) Short-Term Side Effects of CAR T – Cytokine Release Syndrome.  Now let's talk about CAR T-cell toxicities, which are of course very important for any treatment, but in particular CAR T-cells.

There are three specific short-term side effects of CAR T-cells that are considered very, very important and also very specific to CAR T-cells and other types of immune treatments. One of those is cytokine release syndrome.

Cytokines are chemicals of inflammation that develop as the immune system tries to treat the cancer. When these immune cells release chemicals of inflammation called cytokines, a syndrome can develop called CRS, which stands for cytokine release syndrome, that really feels a lot like a case of the flu or COVID-19, or some very inflammatory infectious illness.

Everyone with cytokine release syndrome gets a fever. Other symptoms can be things like chills and muscle aches, significant fatigue, and loss of appetite. In more serious cases, CRS can lead to lowering of oxygen and blood pressure. Very rarely, people need to go to the intensive care unit. In the vast majority of cases, CRS is highly treatable and fully reversible with time.

(00:09:23) Another very important side effect of CAR T-cells is neurologic or brain toxicity. This is also a fully reversible side effect in almost all cases. We don't understand it as well as cytokine release syndrome but most commonly, it tends to affect speech and language. People can have some difficulty with memory and their writing. They can be confused and they can have tremors or some shaking. In more serious cases, there can be very, very significant confusion where people are very sleepy. Very rarely, people have seizures or brain swelling.

(00:10:04) We do have treatments for both of these very important toxicities. For cytokine release syndrome, we typically give anti-inflammatory infusions like tocilizumab, which is a drug that dampens down the inflammation from the cytokine release syndrome. For neurologic toxicity, we typically give corticosteroids, which is a potent anti-inflammatory.

(00:10:26) The reason that we have such specialized monitoring for CAR T-cell therapy patients is because we want to identify these symptoms early and initiate the antidote or treatment for both of them properly. We don't want these things to gallop away from us. We like to have very careful monitoring and treatment for these toxicities. A lot of the logistics of CAR T-cell therapy are designed to protect you by having early identification and management of these toxicities.

(00:10:55) There are some other toxicities that are very important to know about for CAR T-cells. It's very common to have transient lowering of blood counts, and more long-term, lowering of immunoglobulin levels. Immunoglobulins are proteins that the body makes to help clear infections, particularly viral infections.

Because of these lower blood counts and immunoglobulin levels, it's very common for patients to be at higher risk for certain infections, most commonly viral infections, after CAR T-cell therapy. So, it is very important to be aware of this. The treating team is always looking out for infections and monitoring patients over time to minimize the risk of infections. Typically, people will receive vaccines, and some people may need infusions of something called immunoglobulins or IVIG.

(00:11:46) There are also some very rare CAR T-cell side effects that I'd like you to be aware of. One of them is what's called Immune Effector Cell-Associated Hemophagocytic Syndrome (IEC-HS). This is a very specific high degree of inflammation that occurs after the cytokine release syndrome. We'll talk a little more about it. It's really quite rare, but I do want you to be aware that it can occur.

There are reports of second cancers after all treatments, including chemotherapy and CAR T-cells. Second cancers after CAR T-cells are quite uncommon and we'll detail that a little bit more on a subsequent slide.

I also want to talk about an emerging, uncommon side effect that is a movement or neurologic disorder that is different than the neurologic toxicity seen earlier after CAR T.  So, let's talk about each of these rare side effects a little more specifically.

(00:12:48) Immune Effector Cell-Associated Hemophagocytic Syndrome (IEC-HS) What It Is, Who’s at Risk. IEC-HS is a specific inflammation syndrome. It typically occurs after the cytokine release syndrome has finished. We don't fully understand it because it's so rare, but it's thought that a specific immune cell, called a macrophage, becomes very, very overstimulated by the CAR T-cells.

Typically, the main thing we see in this syndrome are abnormal lab tests. We see that coagulation, or the ability of the blood to clot properly, can be abnormal. People typically have very low blood counts for a longer period and a lot of inflammation, either in the liver or inflammation measured by a lab test called ferritin.

What we understand is that the people that tend to be at risk for IEC-HS are those who have a large amount of cancer going into the CAR T-cell infusion. So, we typically try to use that bridging therapy to minimize the amount of cancer that's present before your get your CAR T-cells.

We also understand that certain CAR T-cells can have a higher risk of this. CAR T-cells that generate a lot of inflammation quickly can have a higher risk than other CAR T-cells. But really, across the board for all of CAR T-cells, this is very rare, on the order of 1% of patients. So, I think this is something that you need to be aware of but I don't think it's common enough that it should affect decision-making in most cases. And we do have treatment for it, usually an anti-inflammatory injection called anakinra and steroids.

(00:14:21) Most common symptoms during CAR T-cell therapy. Let's talk some more about symptoms during CAR T. We want to focus on the patient’s experience.

This is a study that looked at the most common symptoms that patients experienced during CAR T-cells. Remember that cancer can cause pain, and sometimes pain can actually worsen when you're receiving CAR T-cells. If you have cancer-related pain and we add in inflammation from the immune system, that pain can actually get worse before it gets better.

Some other common symptoms patients have reported are swallowing difficulties, cough, shortness of breath, and numbness and tingling in the hands or feet.

(00:14:57) This is a separate study that looked at CAR T-cell therapy related symptoms. As you might see in lots of different treatments, the most common symptom was fatigue. Fatigue can be really challenging. If you experience this, you're not alone. Most patients experience fatigue going through cancer therapy, including CAR T-cells.

Other common symptoms reported were lack of appetite, headaches, chills, and neurologic toxicity - confusion and difficulty with memory.

Patients can have pain from cancer and CAR T-cell inflammation. We sometimes see nausea, vomiting, and diarrhea, due to the chemotherapy we give. Patients can experience some dizziness and lightheadedness as they recover from CAR T-cells. So this is a good list of common symptoms that that we might see in someone going through the CAR T-cell therapy process.

(00:15:49) Patients report that physical symptoms after CAR T therapy improve over time.  I've done a study, shown here on this slide, that tried to measure patients' physical symptoms. We asked patients: "Fill out this survey of 10 common symptoms and rate how severe each is from zero to 10, 10 being the worst, zero being no symptom at all." And what you can see is that half of patients reported significant symptoms, symptoms that they rated as a highly bothering them during the CAR T-cell process.

So, about a week after CAR T-cell infusion, half of patients reported a symptom that was severe in nature for them. What we can see is that by one month after CAR T, symptoms had improved. About a third of patients reported severe symptoms. Over time, about a quarter of patients reported severe symptoms.

So, what I take from this is that it's very common to experience physical symptoms, particularly in the first two weeks after CAR T-cells. But it is also very common for people to experience significant improvement of these symptoms, particularly by the time they're three months out from CAR T-cell therapy. Many patients report that their quality of life is improving by the time you get to the three-month mark.

(00:16:54) We also looked at psychological symptoms. Remember this is a complex process. Patients are going through a lot. I mentioned all the different steps of CAR T-cells plus bridging therapy.

We looked at people's symptoms of anxiety, depression, and post-traumatic stress disorder or PTSD. What we saw is that close to half of patients experienced significant symptoms of anxiety, depression, or PTSD as they went through the first month of their treatment, but that the rates of those symptoms improved considerably by the time they reached the three or the six-month time point after CAR T.

However, there is still a minority of patients who have these symptoms at the six-month time point, so one of my goals is to try to design ways that we can continue to improve the symptoms experienced by patients throughout this process. What I want you to take home from this slide is that it's very common for patients to experience symptoms of anxiety, depression and PTSD in the first month, but for many patients, those symptoms improve over time.

(00:18:00) I also want to mention a concept called prognostic uncertainty. What that refers to is not knowing for sure what's going to happen. That's very, very, very common for everybody going through CAR T-cells. Why? Because CAR T-cells are a relatively new treatment. The first approval was 2017. We're not incredibly good at predicting who's going to get the side effects of CAR T-cells and who's going to be cured or have long-term remissions. So, that can create some uncertainty both for doctors and patients as you go through the process.

It's very important to focus on being able to live well and acknowledge the risks and benefits of CAR T-cells. There is some uncertainty right now for doctors and patients about who's going to get side effects, but patients can take heart in the fact that we're very experienced and able to manage these side effects successfully.

(00:19:13) Now let's turn our attention to what happens in the time period after CAR T-cells. So here are some common practices for CAR T-cell patients. Patients are usually followed very, very closely at the CAR T-cell therapy center for the first 30 days after the CAR T-cell infusion. I see patients at least twice a week after they're discharged from the hospital until they're one month out from CAR T-cells. Then I typically see them monthly, and that's pretty standard.

Once you finish the first 30 days of CAR T-cells, we have patients who will go home. Many patients live far away from the CAR T-cell center so we start integrating the follow-up care with the local healthcare team. The teams work together well to integrate that follow-up.

(00:19:59) The reason that the follow-up is so careful in the first 30 days is to make sure that we identify and properly treat the cytokine release syndrome and the neurologic toxicity. Remember, those side effects almost always occur in the first 14 days after CAR T-cell infusion. A nice study documented that it's almost always in the first two weeks. It's very rare after the first two weeks. So that's why the monitoring system is designed to be very careful in the first four weeks to capture those side effects, manage them properly, and have people at a stage where they're very unlikely to occur.

(00:20:37) Care then shifts to a longer-term follow-up after the first month. Because cytokine release syndrome and neurologic toxicity can cause some significant fatigue, it's common for there to be some fatigue and physical stamina recovery that will have to occur well beyond the first month. Fatigue and decreased stamina are very common in the first six months after CAR T-cells and tend to improve over time.

(00:21:02) I would say the most important long-term risk after CAR T-cells, by far, is risk of infections, especially viral infections. So, we typically provide our patients with guidance about vaccinations,  monitoring their immunoglobulin levels, and common-sense precautions like good hand washing and trying to make sure that we're not around people who are sick after CAR T-cells, especially in the early period.

(00:21:28) Several studies have been conducted, including by myself, looking at quality of life over time with CAR T-cells. This chart shows that, over time, patient, on average experience improvements in quality of life after they receive CAR T-cells. That's measured on a score system called the FACT-G.

On average we saw that quality of life declined in the first week after CAR T-cells. Why? Because that's when people are typically experiencing symptoms like cytokine release syndrome, chemotherapy side effects like fatigue and nausea, and potentially, neurologic toxicity.

Most of these side effects resolve by the one-month period. On average, people had a quality of life similar to their baseline at the one-month period.

By the three and six-month time periods, most patients were experiencing improvements in their quality of life.  When we compared quality of life in the three-to-six-month period to the average of the US population it was similar, which I find reassuring. We didn't find any factors that were associated with a poor trajectory. In other words, there wasn't anything that could predict that you were not going to have a good quality of life.

(00:22:49) This is a quality-of-life study looking at a CAR T-cell called liso-cel for patients with lymphoma. Again, this showed very similar things. The red points out improvement. So focus on the red, which is the percent of patients who were having improvement in their quality of life over time. Notice that that red bar number is getting higher and higher as we move out. This study followed patients all the way out to a year and a half after CAR T-cells. What we're seeing is that more and more patients reported improvement in their quality of life the further we get out from CAR T-cells.

(00:23:25) This chart is looking at what we call physical functioning after liso-cel CAR T-cell therapy. So, this is not measuring quality of life but just the physical function of patients over time. And again, you're seeing that the percentage of patients experiencing improvement rises steadily over time .

(00:23:40) Sometimes, we talk about quality of life in other ways, like compared to chemotherapy. A lot of patients who go through CAR T-cell have had chemotherapy before.

This slide compares a CAR T-cell called Axi-cel to a standard chemotherapy regimen. The CAR T is in blue on the left and it's in red on the right. We found that people's quality of life was better with CAR T-cells than it was with standard intensive chemotherapy, and that's been seen in a couple of different studies.

I think the take home here is for lymphoma, we have some evidence that patients who receive CAR T-cells have a better quality of life than those who receive intensive chemotherapy.

(00:24:29) What about multiple myeloma? That's also a very important disease for which people receive CAR T-cells and we see similar things.

This is a study looking at a CAR T-cell therapy specifically for multiple myeloma and we see significant rates of improvement in quality of life, physical symptoms, and physical function as we get to day 100. So again, that three to three-and-a-half-month time point is a very important time when it seems like patients, for the most part, report improvements in their symptoms.

(00:24:59) Now let's turn our attention to survivorship. When we talk about survivorship, we're talking about the long-term experience after CAR T-cells. This is a slide that summarizes all the things we think about. How did CAR T-cell affect you physically and psychologically? How does it affect your  other chronic medical conditions, if you have any? And how do we think about long-term impacts on cognitive function, your ability to think and process information and other cancers?

(00:25:26) This slide summarizes some of the common things patients think about and deal with, and when they occur relative to the CAR T-cell infusion. So, if CAR T-cell infusion is all the way on the left, in the first three months after CAR T-cells, that's where we're predominantly thinking about low blood counts and risk of infection.

Bacterial and fungal infections are things we think about early on when people have particularly low blood counts. Usually, people's blood counts recover by the one, two, or three-month time period.

Then, the predominant infection long-term that we're thinking about are viral illnesses. That's because many patients can have lowering of their immunoglobulins, which are proteins that help fight and remove infections. So, I monitor people's immunoglobulins over the long term to try to understand if that's something that's ongoing for patients.

There are very rare late neurologic events that we're going to talk about on a subsequent slide. And so that's something that we can continue to monitor after the first month and beyond.

Second cancers are very rare, but that's something we're always monitoring for even for years after CAR T-cells.

(00:26:42) I did want to mention leukemia. We've talked about that as another type of cancer where we do use CAR T-cells.

Here's a study that looked at quality of life improvement after receiving CAR T-cells. This is a similar theme to what we saw in lymphoma and myeloma, which is that the vast majority of patients, particularly as we get further and further out from CAR T-cells, report improvements in quality of life, physical function, and physical and psychological symptom burden, which is represented by these bars. Patients in this study were all the way out to three years post to their CAR T-cells.

(00:27:20) So, let's talk about specific survivorship concerns. One study looked at patients who were anywhere from one to five years out from receiving their CAR T-cells and compared them to the general population. Reassuringly, they found no differences in their scores for quality of life, physical health, and mental health.

About a third of patients reported some ongoing cognitive symptoms. However, remember that many patients report some brain fog from chemotherapy, and almost all of the patients studied had multiple lines of chemotherapy.

(00:27:53) I conducted a study looking at people's neurologic function after CAR T-cells. This is a relatively small number of patients. We compared their neurologic function before CAR T-cells and six months after CAR T-cells. We found no difference in their scores either on self-reported cognition or on their performance doing games that tested their neurologic function, compared to before CAR T-cells.

The people that tended to have worsening neurologic function were predominantly people who did not respond to the CAR T-cells, meaning they were getting other treatments for their cancer as well. We do know that accumulating multiple treatments for cancer can be associated with risk of having impairment in our ability to process information.

(00:28:46) Movement and Neurocognitive Treatment-Emergent Adverse Events (MNTs). I've referenced this a couple of times during the talk, but there is some emerging evidence about very rare movement and other neurologic symptoms. The specific name for these is Movement and Neurocognitive Treatment-Emergent Adverse Events, or MNTs. These are neurologic side effects that are different than neurotoxicity. They're things that come later.

The typical two syndromes that people have noticed are some paralysis, or the inability of specific nerves in the face to function. So, something like a facial nerve palsy, meaning that the nerve that moves some of the muscles in the face may not function as well.

Some people have had a syndrome that looks similar to Parkinson's disease, such as trouble with movement and memory, and tremors.

Most patients with these symptoms had CAR T-cells targeting BCMA, which is what's used in multiple myeloma, and most of the reports have been with cilta-cel, a specific CAR T-cell for multiple myeloma. There are very, very, very, rare reports of these symptoms for lymphoma and leukemia patients who had other types of CAR T-cells. At our center we have not seen any cases in patients receiving CAR T-cells for lymphoma or leukemia.

We're still learning about this side effect because it's very rare and it tends to occur later, not in the first 30 days, but usually weeks after an infusion. People who seem to be at risk for this are those with a very high amount of cancer before receiving CAR T-cells; those who experienced high grades of toxicity with the cytokine release syndrome; had neurologic toxicity; and, people who still had lots of CAR T-cells in their body many months later. One study reported that this occurred in about 5% of patients who had received cilta-cel.

We're still developing our ability to treat it. Treatments have usually been steroids and a drug called cyclophosphamide which can lower the number of CAR T-cells in your body. If we do a good job with bridging therapy to keep the amount of the cancer at a lower level going into the CAR T-cells, that should reduce the risk of these toxicities. I think we'll continue to get better at preventing this side effect now that we're learning more and more about it.

(00:31:11) I also mentioned the importance of second cancers. Second cancers are very rare. In one study, they occurred in 3% of cases after CAR T-cells. Remember second cancers can occur from chemotherapy, and everybody who gets CAR T-cells received some form of prior therapy.

The most common cancer that people can have is something called myelodysplastic syndrome (MDS), which is a pre-leukemia that can be a sequela of getting chemotherapy.

There are also a handful of T-cell lymphoma cases that develop after CAR T-cells - five to 10 cases in over 30,000 CAR T-cell treatments. So this is a very, very, very, rare risk.

I think it's important to be aware of it, but I don't think the risk of this side effect is something that typically affects my decision-making about CAR T-cells with patients.

(00:32:06) Lastly, it's very important to note that in CAR T-cell therapy, in order to monitor for the side effects, we require a caregiver for the first four weeks after CAR T-cells. We also ask patients not to drive for the first eight weeks after CAR T-cells, mostly due to potential neurologic toxicity. So this therapy has an important impact on caregivers who are providing very, very important care for the CAR T-cell therapy patient. They help us in monitoring for toxicities.

This obviously is a stressful job and one that affects people's lives. It affects their own health, it can affect their relationships, it can cause financial toxicity. If you're not able to work because you're doing caregiving for that month period, we recognize that that can be very stressful.

(00:32:55) Along with one of my colleagues, Anna Barata, we conducted a study looking at caregiver-reported quality of life and psychological distress. We found high rates of symptoms. So if you're a caregiver and you're experiencing stress and then symptoms, that's very common. We found stress and symptoms in very, very, very, many caregivers going through this process.

I want you to know, number one, you're not alone. And number two, as centers, we're trying to make sure that we maximize resources to support caregivers going through this process.

(00:33:27) So, I want to mention a few concluding points.

Number one, for the studies that we and other groups have done, generally, quality of life and symptom burden improve after CAR T-cell therapy across blood cancers. I find this very reassuring.

Number two, in our studies, quality of life does appear to decrease in the first week or two after CAR T-cells, but by the three-to-six-month period, we're seeing significant improvements in most patients. And from what we've seen in some studies, the quality of life of CAR T-cell therapy survivors seems to match the general population.

Physical and psychological symptoms also improve, although they can persist for a subset of patients, particularly fatigue.

Cognitive problems are a concern. We've mentioned that neurologic toxicity is one of the toxicities. So cognitive outcomes are very, very important, but they appear very good based on the research to date, and it appears that cognitive problems are fully reversible toxicities.

Lastly, caregivers are very important and certainly there's a significant burden on quality of life and psychological symptoms in caregivers. I think we have work to do, as a field, to try to continue to make this as good as possible for both patients and caregivers. And with that, I want to thank you all and I'm super excited for our questions.

Question and Answer Session

(00:34:47) [Susan Stewart] Thank you Dr. Johnson. That was an excellent presentation. We'll now begin the question and answer session.

Joining us for the Q&A session are two additional people who have been through CAR T-cell therapy as patients: Sarah Meredith and Paul Gerhardt.

Sarah retired in February 2022 after 34 years as Professor of Music/Women and Gender Studies at the University of Wisconsin Green Bay. She was diagnosed with high-risk multiple myeloma and had an autologous stem cell transplant in 2019. She had CAR T-cell therapy in May of 2022. She now teaches private voice students in her home studio.

Paul Gerhardt has a master's degree in computer science from Cornell University. He spent his entire career working at Bell Labs leading software development organizations for cellular communications. Paul underwent CAR T-cell therapy in May of 2021 after he was diagnosed with follicular lymphoma. He's now active with summer and winter sports, particularly skiing and tennis, and volunteers to provide support to others through BMT InfoNet’s Caring Connection Program.

(00:36:21) Sarah and Paul, this person wants to know how long it took before you were able to go back to work after CAR T, if in fact you actually did.

(00:36:48) [Sara Meredith] I have a high-risk multiple myeloma and I retired in February '22. In October of '22 I had the CAR T-cell procedure, so it worked out well. I did not go back to work, but I am teaching privately at home now, so I'm living the retired life.

(00:37:21) [Paul Gerhardt] I was retired before I had CAR T, but my experience was consistent with Dr. Johnson's presentation. If I had been working, it would've been at least three months before I would've even considered going back to work on a part-time basis, and maybe six months where I would've felt normal enough to work full-time.

(00:37:47) [Susan Stewart] Is it better for a patient to stay in the hospital during CAR T, or is it better to have CAR T outpatient?

(00:38:05) [Dr. Conner Johnson] So far ,from what we've seen, outcomes are the same for outpatient CAR T-cell therapy and CAR T in the hospital. They both seem equally good. We don't have a criteria for who should do which one, so it's really up to the patient and their doctor. I would trust the CAR T-cell therapy team. If they recommend inpatient, I would do inpatient. If they recommend outpatient, then all the data so far suggests that's very safe.

(00:38:33) [Susan Stewart] Once the CAR T-cells start attacking the cancer, what happens to the byproduct or the waste of the cancer?

(00:38:44) [Dr. Conner Johnson] That's a great question. So, the cancer is basically digested by the immune system - those T-cells and macrophages. It's broken down into its component parts and, basically, you pee and you defecate, and that removes the component parts.

(00:39:08) [Susan Stewart] Paul and Sarah, were there any resources that either the CAR T staff gave to you or that you found on your own regarding information about CAR T and financial issues that were particularly helpful to you when you were going through CAR T.

(00:39:26) [Paul Gerhardt] I would say BMT InfoNet was actually very helpful and comforting to me because a lot of the information that I read was consistent with my experience and helped me feel like, okay, I'm having some problems here and there, but these are common problems and the doctors know how to treat them. So certainly, this website has been wonderful for me and, of course, my care team was always there and always helpful when I had questions.

(00:40:01) [Susan Stewart] Sarah, do you have any other thoughts?

(00:40:08) [Sara Meredith] I just wanted to add that BMT InfoNet connected me to a woman by phone, while I was in the hospital before my procedure, who also had successfully come through the CAR T. And she was in her eighties. She was very positive and she was doing great. It was a very positive activity for me, so I thank BMT InfoNet for that.

(00:40:34) [Susan Stewart] Is CAR T brain different from chemobrain?

(00:40:44) [Dr. Conner Johnson] It is. Chemo brain is very, very common and people generally report a fogginess related to that.

CAR T-cell therapy neurotoxicity has a very different impact on people's thinking. There's a very, very potent language and writing predilection, so it's very common for people to have trouble with certain words or to have trouble with their writing or with recognition of things. And so it's a very specialized type of neurologic side effect.

The good news is that this is highly treatable and reversible in almost all cases without long-term sequelae, although some people have reported memory difficulties that persist for a few weeks to months after CAR T-cells.

(00:41:36) [Susan Stewart] This question is from the spouse of a patient. “In 2022, my husband was part of a CAR T clinical trial for mantle cell lymphoma. The clinical trial is running for 15 years. What happens if a recurrence occurs during that time?”

(00:41:54) [Dr. Conner Johnson] So, for mantle cell lymphoma specifically, there are quite a few therapies that are approved in the post CAR T-cell setting. It would depend on exactly what treatments he's had in the past. Many people use a drug called pirtobrutinib or other medications that have been approved over the last few years for mantle cell. There are still quite a few treatments available for mantle cell even in the post CAR T-cell setting.

(00:42:19) [Susan Stewart] Next question: "My wife has multiple myeloma. She had CAR T 27 months ago and has been treatment free ever since. Her numbers are starting to rise though, and it's anticipated she'll need to restart treatment soon. What treatment options are available to her after CAR T?"

(00:42:42) [Dr. Conner Johnson] It really depends on what her prior treatments were. There's a whole class of medications for multiple myeloma called bispecific antibodies. It would depend on what treatment she's had in the past, but that may be one class of medications that your treating team would consider using. There are multiple bispecific antibodies approved for multiple myeloma and they're an immunotherapy that targets the immune system.

(00:43:12) [Susan Stewart]  For Sarah and Paul:  “Thinking back on your CAR T-cell experience, is there anything you would have done differently to prepare for it?”

(00:43:25) [Sara Meredith] I was part of a trial and their idea was not to go on bridging therapy if possible. I had a great deal of multiple myeloma present in my body and if I did this again, I would certainly ask to have the bridging therapy earlier. I went into the procedure with quite a bit of myeloma present, which I think affected my CRS reaction, but that's probably the only thing.

(00:43:54) [Susan Stewart] What about you, Paul? Anything you would've done differently?

(00:43:59) Paul Gerhardt; I can't really think of anything, no.

(00:44:02) [Susan Stewart] What helps people who do not develop immunity a year after CAR T?

(00:44:15) [Dr. Conner Johnson] So, when we talk about developing immunity, that's a pretty complicated topic. You can have immunity for some things and not for other things.

The development of immunity is a long-term process. Certainly, regaining immunity after CAR T-cells is gradual. What we try to do post CAR T-cells is monitor the recovery of the immune system. We do a complete blood count with differential, and we typically measure immunoglobulin levels.

If people are feeling well even if they have low immunoglobulin levels, I typically don't give them immunoglobulin replacement. What I do is I make sure people are vaccinated for common infections- RSV, COVID-19, influenza, pneumonia. If people develop recurrent infections, I often will start giving immunoglobulin replacement with something called IVIG. Those are probably the most common things that we do in terms of trying to think about the immune system recovery and modify it.

(00:45:22) [Susan Stewart] “My daughter had all of the severe life-altering effects from CAR T-cell therapy for multiple myeloma. She's had Parkinson's-like symptoms for over a year and she had all of the symptoms you mentioned in your talk. She's wondering if there's any hope for recovery at this point.”

(00:45:44) [Dr. Conner Johnson] First of all, I'm so sorry for what she's gone through. We simply don't have a ton of information about what the long-term recovery is from Parkinson's symptoms after CAR T. I can say we've had patients who have very good recoveries at our own center, but there's not really a study or a trial yet that's been able to put a number on that. So what I would say is to continue to follow closely with the CAR T team, and hopefully with time there will be continued improvement.

(00:46:17) [Susan Stewart] How long do the modified CAR T-cells stay active in your body?

(00:46:23) [Dr. Conner Johnson] It varies considerably. We don't yet have an FDA-approved test to measure them, which I find frustrating as a treating physician. In studies it can range from months to years. Some of the original CAR T-cell recipients from the trials from years ago actually still have CAR T-cells circulating, so these can persist for long, long periods of time.

We actually don't know what the right amount of time is to get the best response. In other words, you might think that you want the CAR T-cells to be around as long as possible, but we actually don't know if that's true. We have not figured out yet how long CAR T-cells need to be around to get the maximal response for different types of diseases. But the short answer would be that these can be around for years.

(00:47:16) [Susan Stewart] For patients who work a flexible remote job, do you recommend that they still take leave versus continuing to work during CAR T-cell therapy? And if you recommend that they take time off, how long?

(00:47:32) [Dr. Conner Johnson] I would usually take time off because if you develop neurologic toxicity, which hopefully you won't, it's hard to work with neurologic toxicity. You want that to be fully recovered. I typically have people take four weeks off from the time of infusion and then make a decision based on how the recovery period is going. Remember, most of these side effects are in the first two weeks. It's uncommon for these side effects to recur or occur after two weeks have gone by. So you do tend to get a good sense of where things are going as you approach that one-month time period. So, I think for most people, taking that month off is advisable.

(00:48:19) [Susan Stewart] How long does CAR T-cell therapy control multiple myeloma?

(00:48:28) [Dr. Conor Johnson] Some patients remain in remission for several years after receiving their CAR T-cell infusion. The average length of remission differs based on which CAR T-cell therapy you received. The two CAR T-cells that are approved for myeloma - cilta-cel and ide-cel - have not been compared head-to-head in a randomized controlled trial. In general, the average length of remission was longer with cilta-cel, but those two therapies have not been compared to head-to-head. On top of that, we've got lots of multiple myeloma CAR T clinical trials that are coming, so we'll see what the length of remission is for those CAR T-cell products as well.

(00:49:08) [Susan Stewart] Sarah: You've had both an autologous stem cell transplant and CAR T-cell therapy. How would you compare the experience with both of them? Was one harder than the other? Were they similar?

(00:49:24) I would say that the duration of recovery was harder for me with the stem cell transplant. But because I reacted so severely to the CRS, maybe the first two-to-three months were more difficult with the CAR T-cell. But for me it was well worth it. I got cataract surgery, hearing aids and dental work done during my months after the CAR T-cell that I could not have done when I had the cancer present. So it was very valuable and I lived it to the utmost.

(00:50:02) [Susan Stewart] A question for Paul:  How many times did you relapse before you had CAR T-cell therapy for follicular lymphoma? Have you been told that your CAR T-cell therapy is a cure for you?

(00:50:33) [Paul Gerhardt] I had two relapses before CAR T. My healthcare team has always hesitated to use the word cure. I'm very, very happy to be in remission after three and a half years and that's good enough for me. I just don't think about whether it's a cure or not.

(00:51:03) [Susan Stewart]  Can you have more than one CAR T-cell therapy and under what circumstances?

(00:51:12) [Dr. Conner Johnson] That's a terrific question. The answer is, in general, repeatinf CAR T-cell therapy with the same protein target - so the same latch - has not had very good results. However, there are many, many, many clinical trials testing new and different types of CAR T-cells, and that you absolutely can do.

For example, if you had lymphoma and had CD19 CAR T-cell, and later on thought of doing a clinical trial CAR T-cell targeting different proteins like CD22 or CD79, that strategy is absolutely being pursued by plenty of patients in clinical trial settings across the United States and beyond.

(00:52:07) [Susan Stewart] After taking part in the CAR T clinical trial, how long does it take to be in remission?

(00:52:24) [Dr. Conner Johnson] Typically, we’ll assess the response 30 days after a CAR T-cell infusion. In all of the six CAR T-cell products that have been FDA-approved, most patients have a response at that time point. That doesn't always mean that it's going to be the peak response. Remember when we think of response, we think of the cancer shrinking after getting the treatment and that's different from the best response. In other words, how much shrinkage do we get? Sometimes the best response takes more than one month to achieve, but most patients do get a response by that thirty-day time point.

(00:52:58) [Susan Stewart] Do you see greater cytokine release syndrome and neurotoxicity issues with people who have autoimmune diseases like rheumatoid arthritis?

(00:53:11) [Dr. Conner Johnson] There's been no association of autoimmune disease with augmenting the risk of these toxicities. The main risk factor for having these toxicities that's been identified is the type of CAR T-cell therapy you get. That's why it's good to talk to your team about which CAR T-cell therapy you're getting and why, and how much of the cancer you have going into the treatment.

(00:53:37) [Susan Stewart] Do you recommend similar vaccination guidelines as those followed after a stem transplant or are there different ones that you recommend for CAR T patients?

(00:53:49) [Dr. Conner Johnson] There are different standards at different institutions and I'm not sure there's one right answer that we've identified yet. My own practice is that after three months, I vaccinate for COVID-19 and influenza because those are two common viral illnesses that we don't want people to get. Over the long term, I make sure people have been vaccinated for shingles, RSV, COVID-19, and bacterial pneumonia. I do not do a full transplant revaccination series.

Mmany people who go through a transplant will have a two-year period where they get multiple vaccines to be fully vaccinated, much like in childhood. I do not do that for CAR T-cell patients because it's not a transplant. You don't have your full immune system wiped away. You're getting a genetically engineered targeted CAR T-cells. So, I do vaccinate but not to the same degree as after a transplant.

(00:54:56) [Susan Stewart] If a person is taking medication to keep depression and anxiety under control, will affect the risk for CAR T side effects?

(00:55:09) [Dr. Conner Johnson] It shouldn't. There's really no association between antidepressants and the risk of CAR T-cell therapy, neurologic toxicity, or persistent toxicities with CAR T-cell. I think it's perfectly safe to continue those medications.

Some people are on benzodiazepines. That's a medicine like Ativan which they take for a panic disorder or for other things. That medicine can depress thinking. It can affect how quickly people respond to certain statements. So benzodiazepines may be held during the course of the CAR T-cell therapy hospitalization just so that neurologic toxicities can be recognized.

(00:55:51) [Susan Stewart] Are there any bone problems after CAR T?

(00:55:59) [Dr Conner Johnson] When we talk about bone problems, usually we're asking "Are there issues with bone density after CAR T-cell therapy?" To our knowledge, CAR T-cell therapy should not have a major impact on bone density. But if you're on a protracted course of steroids to manage the side effects, that could affect bone density.

Most of the time with these toxicities, we don't need to use a lengthy course of steroids. But if you did need a longer course of steroids, I would think about bone health and make sure that it's being monitored properly. Patients with multiple myeloma commonly have an impact on bone health just from the myeloma, so their doctors are always monitoring bone health and making sure that it's being properly managed.

(00:56:42) [Susan Stewart] What percentage of patients do not achieve remission after CAR T-cell therapy for multiple myeloma?

(00:56:51) [Dr.Conner Johnson]That depends on which CAR T-cell therapy  you're receiving. Some of the CAR T-cell therapies have remission rates that are around 90% with CAR T-cell. So that means that the vast majority of patients do achieve a remission with treatment.

(00:57:10) [Susan Stewart] Can I start CAR T-cell therapy before I come out of remission?

(00:57:21) [Dr. Conner Johnson] You mean as a preventative measure before you relapse. That's another great question. So far, there are two answers to that. If someone had first-line therapy for diffuse large B-cell lymphoma and they're in remission, there's no CAR T product that the FDA has approved to give in that situation outside of a clinical trial.

However, sometimes patients will receive bridging therapy and go into remission from the bridging therapy. In that situation, we can still give the CAR T-cells.

In other words, if you've received first-line chemotherapy and you're in remission, we don't give CAR T-cells. But if we're doing bridging therapy and there's a remission, we still give the CAR T-cells.

(00:58:25) [Susan Stewart] This gentleman had CAR T October 2, 2024 for diffuse large B-cell lymphoma. He still has lots of nasal and cough expectorant. Is this normal? Should the amount of mucus be concerning?

(00:58:53) [Dr. Connor Johnson]Obviously, a doctor doing an evaluation of things is better than us on the call, but I've got to tell you, many patients have recurrent viral upper respiratory tract illnesses after CAR T-cells and it often has to do with those low immunoglobulins that we talked about. So, I don't consider it concerning that there's a lot of mucus and some recurrent viruses. That's just very common from the low immunoglobulins. Mmost likely, it's just going to take time for immunity to build.

My strategies for these is, number one, I try to make sure that people are well vaccinated for the common things that cause this stuff. You know, RSV, flu, and these other viruses, the pneumonia vaccine called Prevnar. And then secondly, if you're getting recurrent viral illnesses and lots of mucus production, just ask the medical team what they think about immunoglobulin replacement with IVIG if that's not been done.

(00:59:49) [Susan Stewart] For Sarah and Paul: Were there were any complimentary therapies like exercise or yoga or anything of that nature that you used to help you recover after CAR T?

(01:00:09) [Paul Gerhardt] I have always been a very active person so as soon as I could, I started exercising on my own. I had opportunities to do that in my care team setting, but I just chose to do it on my own. I felt it was very important for me to do that, and I could tell on my own what I was capable of and what I wasn't. So I started out walking to the kitchen and then walking to the mailbox and then walking down the block, and I just built up on my own and am now almost back to where I was before CAR T.

(01:00:54) [Susan Stewart] Great. What about you, Sarah? Were there any complimentary type therapies that helped you recover?

(01:01:02) [Sara Meredith] Yes. Just like Paul, I started out with a little bit of walking and then increased. I did so many steps on my Fitbit every day, trying to increase it every day. We walk our dog daily, and so I started out walking very short distances and increased it up to two miles, which was amazing. I also eventually did, chair yoga, which was good. Tai Chi is also excellent for balance and helped me regain some of those items that I'd lost.

(01:01:43) [Susan Stewart]  Is there a certain diet one needs to follow after CAR T?

(01:01:50) [Dr. Conner Johnson]There's no special diet. The one thing I would say is if you're neutropenic - neutrophils are a type of white blood cell that can be lowered in a minority of patients - then I usually have patients be careful about raw meat and well water because there can be bacteria in those items. Most patients are not neutropenic after CAR T-cells and so there'd be no dietary restriction whatsoever.

(01:02:19) [Susan Stewart] Paul or Sarah, did you have any dietary restrictions?

(01:02:25) [Sara Meredith] Yes, I was neutropenic for a short time, but I would say that I have changed my diet quite immensely. I eat mostly a plant-based diet. I grew up on a farm so I'm used to eating a lot of beef and red meat, but I've cut back a lot on that and increased fruits and vegetables quite a bit.

I'm currently on Talvey after my relapse, which restricts my diet even more because you lose some appetite, and so I've changed my eating immensely since my CAR T.

(01:03:19) [Susan Stewart] Paul, did you have any dietary changes?

(01:03:22) [Paul Gerhardt] My only challenge to be honest, was to get enough calories to gain some weight. I lost weight through all the chemo and the CAR T and everything and I didn't have a lot of that to begin with. So my only dietary challenge was eating stuff that I wouldn't normally eat like fettuccine Alfredo, because it has so many calories, to just try to get my weight back up.

(01:03:53) [Susan Stewart] What help is available for people who do not recover immunity after CAR T?

(01:04:03) [Dr. Conner Johnson] So, in terms of what options are available for patients who've had multiple myeloma or lymphoma and had a stem cell transplant in the past, you can ask your doctors whether there are any leftover stem cells that could be given. That has not been studied in a clinical trial, but is something we can think about. If you're someone who has never had a transplant and there are no stem cells, probably the main piece for immunity is thinking about vaccination and IVIG, which is immunoglobulin replacement therapy.

(01:04:40) [Susan Stewart] Does low IGG cause fatigue?

(01:04:48) [Dr. Conner Johnson] Typically, we don't think of it in and of itself causing fatigue, but remember, that does put you at risk for recurrent viral illnesses which absolutely will cause fatigue. So indirectly, yes.

(01:05:02)[Susan Stewart] How can you conquer fatigue after CAR T-cell therapy?

(01:05:08) [Dr. Conner Johnson]I  think this is one of the hardest things about CAR T-cells and cancer therapy in general. We don't have a one size fits all approach for fatigue, but some important principles are the following:

I think it is critical to ensure that there is a physical activity regimen in place in order to facilitate recovery. I think Sarah gave some excellent examples of physical activity regimens.

It's also very important when you institute a physical activity program that you don't have major ups and downs. Some people will have a day where they feel okay and then go all out, and then they'll crash and have a day where they don't do anything, This up and down will perpetuate fatigue. So some of the best things for fatigue are consistent physical activity that builds slowly over time.

(01:06:02) [Susan Stewart] Is getting spinal surgery discouraged after CAR T-cell therapy?

(01:06:10) [Dr. Conner Johnson] There's no specific contraindication or problem with getting spinal surgery after CAR T-cell therapy unless there are persistent low blood counts. Remember, for any surgery, a good platelet count is very important for ensuring safety. Platelets are cells that protect you from bleeding. So that's probably the primary thing that we want to make sure has recovered.

Secondly, we mentioned neutrophils. Neutrophils are a type of white blood cell that protect against bacterial infections and we'd love to have recovery of those cells before going through a surgical procedure

(01:06:57) [Susan Stewart] Paul and Sarah: Did you have any unexpected complications after CAR T? Paul, I believe you told me that you had some skin cancer. Do you want to talk about that?

(01:07:12) [Paul Gerhardt] I did. I had many of the things that Dr. Johnson listed as most common, but the one that maybe is a little less common, I guess, is I had multiple skin cancer experiences. I never had it before CAR T, so I don't know if it's a cause and effect thing or not. But after I had CAR T, every time I went to the skin care doctor there was more cancer, more surgery, multiple times. And just six months ago, after three years of that, I went to the skin cancer doctor and had a clean bill of health with no additional cancer.

(01:07:58) [Susan Stewart] What about you Sarah? Were there any unexpected side effects after your CAR T?

(01:08:06) [Sara Meredith] Not really. I experienced mostly what I expected. I had one bout with RSV, which was rigorous, but I recovered. In general, I had planned out what I was going to do after I was chemo-free and cancer-free, so it was a joy to be in that condition.  I had plenty to do, but I really didn't have any setbacks, I would say.

(01:08:38) [Susan Stewart] Why CAR T isn't used more widely in patients with leukemia like AML?

(01:08:47) [Dr. Conner Johnson] For AML, which is acute myeloid leukemia, doctors and researchers are trying to identify a CAR T-cell therapy strategy that is effective in AML. It's been a little bit harder developing CAR T-cells in AML because the cancer cell is a myeloid cell, and these cells are absolutely integral to protecting from all kinds of infections. So it can be trickier developing a CAR T-cell treatment in that scenario, but there are many clinical trials ongoing, and hopefully, eventually, we'll develop a CAR T-cell that targets AML.

(01:09:33) [Susan Stewart] How does having high-risk myeloma affect CAR-T treatment? Is the treatment different if you have high-risk myeloma as opposed to less high-risk?

(01:09:58) [Dr. Conner Johnson] High-risk myeloma may have a higher tumor burden and so we certainly think about the amount of tumor being an important component for the risk of toxicities and response to therapies. That’s probably the number one thing that we think about. I'm not a myeloma specialist per se, I'm a lymphoma specialist, although I do give myeloma CAR T-cell therapy. I think about high-risk myeloma as always being something that we worry may not have as good of a response because of how much disease there could be.

(01:10:36) [Susan Stewart] Sarah, did you have anything you wanted to add to that?

(01:10:40) [Sara Meredith] Well, I think that having high-risk myeloma probably had something to do with my having just an eighteen-month period of being chemo-free and cancer-free.  But I would certainly do it again. If I had a chance to have the CAR T I would do it again.

(01:11:04) [Susan Stewart] Do you know of any young people who went through CAR T-cell therapy and had children after that?

(01:11:24) [Dr. Conner Johnson] There's no study, but I have had patients who have had children after undergoing CAR T-cell therapy and have had good pregnancy outcomes. I'm hoping that we'll get a nice study that'll be able to give us numbers on those types of things. CAR T is a relatively new treatment, so we just haven’t had enough time to have a good study on fertility post-CAR T-cells. But anecdotally, I have had patients have healthy pregnancies afterwards.

Now for any individual patient, when we talk about fertility, it's very important to talk with the treating team. Remember fertility integrates lots of different things including what bridging therapies have been given and all kinds of stuff like that. So it's very important to talk with the treating team about the specific situation. But we have had patients have healthy pregnancies after CAR T-cells.

(01:12:16) [Susan Stewart] If someone has multiple myeloma and prostate cancer and undergoes CAR T-cell therapy for myeloma, will that have any effect on the prostate cancer?

(01:12:28) [Dr. Conner Johnson] Yeah, that's very, very good question. There is some concern that if we give a treatment that lowers the immune system, the other cancer could potentially take advantage of that. So, if the CAR T-cells lower the immune system, maybe the prostate cancer would have an opportunity to grow. That is a theoretical concern of the CAR T-cells. And we've talked about how rarely there are second cancers after CAR T-cells.

That said, there's nothing that says that you can't get CAR T-cells when you have prostate cancer. Perfectly fine to go through CAR T-cell therapy for myeloma while having prostate cancer, but it is important for the teams to talk to each other. So if you have a myeloma specialist and a prostate cancer specialist, we are going to want to have monitoring of the prostate cancer after your CAR T-cells. As long as everybody's working together, that's not a reason not to go through CAR T-cells.

(01:13:31) [Susan Stewart] Sarah, what kind of treatment did you go on after you relapsed after CAR T-cell therapy, and has it been effective for you?

(01:13:44) [Sara Meredith] Since June, I have been on Talvey, and it has been effective in that my blood numbers are stable and that's very positive. There are some uncomfortable side effects from it, but I have dealt with each one. I have to rise to the occasion. But definitely, it has helped. It's maintaining my blood numbers, so I've had a really good outcome of it so far, so I'm happy about it.

(01:14:21) [Susan Stewart] Paul, you've not relapsed. Are you finding yourself taking fewer medications since CAR T or more?

(01:14:30) [Paul Gerhardt] I take basically nothing. So I haven't had any bad situation related to medications due to CAR T.

(01:14:42) [Susan Stewart] All right, this will be our last question. Are there any guidelines about post-CAR T care, particularly when people go back home to their local physician?

(01:15:01) [Dr. Conner Johnson] There's not really an established single guideline on what to do in the post-CAR T-cell care. I've actually suggested that we write these and establish clear guidelines. The most important thing, in my opinion, just ongoing communication between both teams. There's a lot of experience with patients transitioning from their CAR T center to their local team and I think we do a great job of that.

(01:15:38) [Susan Stewart]  All right, well on behalf of BMT InfoNet and our partners, I'd like to thank Dr. Johnson and Sarah and Paul for an extremely helpful presentation, and question and answer session.

And I do want to give a shout out to Bristol Myers Squibb, whose generosity allowed us to have this webinar today.