Protecting Your Health after CAR T-cell Therapy

Transcription:

[00:05] Moderator: Speaker Introduction. Welcome to the workshop, Protecting Your Health after CAR T-Cell Therapy. My name is Becky Dame, and I will be your moderator for today's workshop.

It is my pleasure to introduce today's speaker, Linda Ramsdell.  Ms. Ramsdell is the Assistant Director of the Immune Effector Cell Therapy Program at Dana-Farber Cancer Institute, where she provides patient education and emotional support to patients and families, fostering a holistic care environment.

She has been involved in research and presentations at medical conferences on outpatient CAR T-cell programs, the late effects of CAR T-cell therapy, and the latest advances in CAR T-cell therapy. Please join me in welcoming Mrs. Ramsdell.

[01:04] Linda Ramsdell: Thank you. I'm very excited to talk to you all today about protecting your health after CAR T-cell therapy.

[01:21] These are the learning objectives I hope to cover today.

[01:28] We're going to discuss quality of life after CAR T-cell therapy, potential late and long-term effects after CAR T-celltherapy, both psychological and physical, incidence and risk factors for late and long-term side effects after CAR T-cell therapy, self-monitoring for late and long-term side effects, to whom and when to report symptoms after CAR T-cell therapy, and lifestyle changes that can prevent and or manage long-term effects of CAR T-cell therapy.

[01:34] So when we think about quality of life after CAR T-cell therapy, generally we think that you're going to have a really good quality of life.

[01:59] Most patients feel the side effects or the symptoms of CAR T-cell therapy after the lymphodepleting chemotherapy and up through the first 30 days after their CAR T-cells are infused. Then those symptoms tend to subside.

So, when I have a patient in front of me, and maybe they're 15 days out, they may not be feeling great, but they're usually feeling better than that immediate period after the CAR T-cell infusion.

Most of my patients tell me they have significant fatigue and decreased stamina.

Some patients  have pain, and other patients report that they have sleep disturbances. Sometimes patients can get into this tricky cycle of napping during the day and not sleeping at night. 

And then, when we think about cognitive functioning, we think about your attention and memory, and how you are going to transition back to work, if you are going to work, when you're having some of those symptoms.

We think about your emotional health. What is your anxiety level, your depression level, do you have any fear of relapse, and how is your social functioning?

When you're getting back out after your CAR T-cell therapy, what are those relationships in your social life like, the intimacy, and the caregiver burden?

We also have to think about financial toxicity because these therapies are very expensive, and accessing the care can be very expensive as well. And then long-term supportive care.

[03:50] So in the early period, those first weeks to first three months, your quality of life may dip. That's due to the acute effects after CAR T-cell therapy that pop up immediately. When we talk about acute, we're referring to the immediate period after CAR T-cell infusion.

[04:02] We’re also thinking about the effects after being hospitalized. So, some of that deconditioning or feeling really easily fatigued after your hospitalization.

[04:15] After six months, we expect that your symptoms are going to improve pretty drastically. 

While some patients may have persistent fatigue, cognitive symptoms, and infection burden, these generally improve with time.

[04:34] What are the risk factors for having a better or worse quality of life after CAR T-cell therapy?

We're looking at the patient's ability to care for themselves and perform their daily activities prior to CAR T-cell therapy. Are you able to do these now? Was it already tough prior to CAR T-cell therapy? That's going to help determine who may have a better or worse quality of life.

If you have other comorbidities or other health issues before CAR, that's going to impact your quality of life. after.

How many prior lines of therapy you've received before CAR T-cell therapy can also impact your quality of life. 

We're looking at how sick you were when you came in. Did you get a ton of chemo before?  Are you already feeling pretty deconditioned? All of that could affect your quality of life after CAR T-cell therapy.

How well the CAR T-cells work is going to affect your quality of life after CAR T-cell therapy.

If you have ongoing low blood counts or infections, that's going to affect how you're feeling.

Persistent neurologic symptoms, and whether you have psychosocial support, are going to affect how you're feeling after CAR T-cell therapy.

So when we talk about CART-cell therapy, it's actually hard not to talk about the early toxicities when we're talking about long-term toxicities.

[05:52] When we talk about early toxicities, we're talking about toxicities within that first month after CAR T-cell therapy. These are generally due to the chemotherapy you received before your CAR T-cell infusion.

There's lymphodepleting chemo that you'll get before your infusion, and you can get side effects from that. We're not necessarily giving the chemotherapy to treat your disease itself, rather, we're making your body a favorable environment for those CAR T-cells to go into, but those chemotherapies still have side effects.

[06:13] The early side effects seen after CAR T-cell therapy include cytokine release syndrome (CRS), immune effector cell-associated neurologic symptom (ICANS), and immune effector cell-associated lymphohistiocytosis-like syndrome (CHS .

ICHS is like a very, very, very robust cytokine release syndrome. It's uncommon but serious, and it's very, very treatable with prompt recognition.

[06:58] We also think about infections in that early period after CAR T-cell therapy because we are giving you that lymphodepleting chemotherapy.

We are going to potentially make you cytopenic, so you're going to be at risk for infection. We usually give preventative antibiotics for that.

[07:12] So when we think about cytokine release syndrome, it is not unique to CAR T-cell therapy, but it is very common after CAR T-cell therapy.

The proliferation of CAR T-cells increases the number of inflammatory cytokines in your body. So, the CAR T-cells are attacking your cancer, and there’s a spillage of all these cytokines into your body.

You're getting all this inflammation, which is the point of doing this; we're causing all of this inflammation in your body so that it's attacking your cancer.

It is very, very common to have CRS. About 40-90% of patients develop CRS.

Certain CAR T products are associated with higher rates of CRS. So, we may see a higher rate of CRS with one specific product, but maybe it's not as high a grade.

Most cases of cytokine release syndrome are mild to moderate. CRS is very, very, very treatable. We have really great things to treat CRS now.

The duration of CRS is really variable. It's product-dependent. Each individual product has a known timeline in which CRS typically begins.

[08:41] The typical symptoms of cytokine release syndrome (CRS) are fever, and it can be only a fever, malaise, headache, rigors, - those shaking chills, and nausea.

It may just be flu-like symptoms where you're not feeling great because you have a fever, or it can progress to more significant symptoms, like low blood pressure, low oxygen levels, and electrolyte imbalances. That's when we'll start thinking about intervening with some medicines.

[09:16] During CRS, we see an elevation in your blood inflammatory markers. We look at a couple of different markers. One is called CRP. Others are ferritin,  procalcitonin, and IL-6. Some institutions may not do an IL-6 and only do a CRP, but basically, these tests show different levels of inflammation in your body.

If we start to see these numbers rise and spike, it gives us a clue that CRS is either starting or has already started.

[09:51] Sometimes patients need ICU-level care, but it's far less common now than it was when CAR T-cell therapy first started,

We're more comfortable now intervening sooner with tocilizumab and or steroids than we were before.

We know certain products act a certain way, and when we're thinking about the CRS incidence, all of these different products have an average amount of any grade CRS, which could be grade 1, 2, 3, 4.

If you're grade 1, you only have a fever.

If you're grade 4, that's when you're probably in the ICU. You're really feeling terrible, and you need multiple medications to help support you.

[10:37] You can see on this graph the various CAR T-cell products. The purple bar is any grade of CRS, and that lighter blue number is severe CRS,when you need to go into the ICU.

A lot of patients who receive axi-cel will get CRS, but not a ton of patients get that high grade. CRS. 

So, having the high-grade CRS is far less common, but having CRS is actually pretty common.

These are all of the commercially available CAR T-cell products that may be offered to you. They all have different indications, but your provider will find the one that is the best fit for you.

[11:24] Another side effect that we typically talk about is something called neurotoxicity or ICANS.

This occurs when cytokines or CAR T cells cross the blood-brain barrier and wreak a little havoc on your neurological system. It can affect 20-60% of patients and typically occurs after the onset of CRS. It can occur independently of CRS as well. Even if you've never had a fever, sometimes you can get the neurologic effects.

It can last from days to weeks. It really just depends on what's going on inside of your individual body.

Most cases resolve with treatment, which is usually steroids.

The symptoms can be mild to severe. Sometimes it's just a little bit of forgetfulness. We might notice that a patient is having a little more difficulty navigating on their phone. Maybe they were trying to say one word, and they said something else instead. It can progress to things that are much more serious, like seizures and swelling as well.

We use a standardized tool to assess memory and cognition when we're considering how to grade ICANS.

The treatment is steroids. Most cases are reversible. But some cases will need ICU-level care.

[12:58] As shown on this slide the incidence of ICANS is going to vary, depending on the CAR T-cell product.

The purple bar on the left represents any grade of ICANS. It can include the lower grades one and two, as well as the higher grades.

The light blue bar on the right represents the more severe ICANS, grades three or four. Grade four is when you are probably in the ICU.

The numbers are a little less than what we saw with CRS for the same products, but it's something we're going to carefully monitor and intervene in.

[13:45] When we think about toxicities between days 29-100, we think about infection risk and delayed neurologic problems.

Infections are pretty common after CAR T, mostly viral infections.

You can have delayed neurologic problems, which are very, very, very uncommon. They can include headaches, tremors, and cognitive changes. Some patients develop a Parkinson-like syndrome as well.

Sometimes patients need blood transfusions or growth factors after CAR T-cell therapy. Very rarely would we need to do something beyond that.

It's very common to develop hypogammaglobulinemia, an abnormally low level of antibodies in the blood. It impairs your body’s ability to fight infection. It results from the destruction of normal B-cells, because that's what the CAR T-cells target. We think of it as collateral damage.

If you're getting any product for, say, lymphoma, we're going to affect both the malignant B cells and the healthy B cells, unfortunately.

It affects the majority of patients and can persist for months to years, but there are things we can do to help with that as well.

[15:17] Long-term, persistent low blood counts are very common. 

It is caused by a mix of factors: sometimes prior lines of therapy, how much chemo your marrow is exposed to in addition to the lymphodepleting chemotherapy, and sometimes just the immunosuppression from the CAR T-cells. 

[15:33] You may have a weakened immune system.

 It is very common to have B-cell aplasia because the CAR T-cells target B-cells, whether they're cancer cells or healthy B cells. 

That results in low antibody levels. Antibodies help your body recognize viral infections and other foreign substances. It can persist for years.

[16:03] Neurological and cognitive effects are very common. You may have difficulties with your memory, attention, or information-processing speed.

[16:17] There are also cardiovascular effects that we can see after CAR T-cell therapy. It's primarily in people who have had a really severe form of cytokine release syndrome.

[16:29] You can also get secondary cancers. They are extremely rare, but there's always a small risk of this side effect. Potentially, you may develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or a T-cell lymphoma.

[16:43] Psychological or psychosocial effects are common. They can present as anxiety or depression, and be precipitated by financial strain or even relationship changes, and the burden on our caregivers.

[17:04] Long-term monitoring after day 100 is usually about every three months.

Every institution has its own timeline for when it wants to see you, but generally, we see our patients every 3 months after they receive CAR T-cell therapy.

[17:20] After you hit that one-year mark, monitoring is usually annually.

The things that we look for are: Do you have infections? What's your immune status? 

Do you have hypogammaglobinemia or low immunoglobulins in your body? Those are like memory-cell antibodies that help you fight off infections.

Do you have CAR T-cell persistence? Do you have any new malignancies or secondary cancers, ongoing neurologic complications, or cardiovascular complications?

If you had one of those really severe CRS syndromes, what's your respiratory status, your GI status, and how is your liver looking? Does it look happy after CAR? Did it get a little inflamed?

[18:07] There can be late effects of CAR T-cell therapy on the bone marrow. 

You can have low blood counts. After your CAR T-cell therapy, low blood counts may persist and never fully recover. They may come up, then dip down again. 

We've talked about B-cell aplasia. That is the low level of B-cells that make antibodies. When you have low antibody levels, you have hypogammaglobulinemia.

You may have had IVIG before, depending on which disease you're being treated for. It is something else we can restart after CAR T-cell therapy or newly start. It’s an IV infusion, typically given monthly. You can have delayed B-cell or T-cell recovery.

[19:07] You can have bacterial infections or viral reactivation late after CAR T-cell therapy in select patients, as well as nasty opportunistic infections that we don't want anyone to get.

We can give antimicrobial prophylaxis, or we can give you some antimicrobials, like an antifungal or an antiviral, after CAR T-cell therapy to help prevent infections, almost like boosting your immune system a little bit as part of your survivorship care.

[19:46] In the first 30 days after CAR T-cell therapy, that's when you have the highest risk for things like bacteria in your blood or bacteremia.

Also, gastroenteritis, diarrhea, or infectious diarrhea. Pneumonia can also be more common in that particular period when your cell counts are really at their lowest.

You can have viral reactivation with shingles or chickenpox. You can get some of those seasonal respiratory viruses during the first 30 days.

During those first 30 days, you're more likely to get candida infections because of your counts being low and being a little bit more susceptible to mold infection.

[20:41] Once we get beyond that one-month period, that's when we're seeing things like seasonal viruses, pneumocystis pneumonia, and mold infections.

Up to 6 months after CAR T-cell therapy, we're not taking you off any prophylactic medications and are monitoring your CD4 counts. Most institutions keep it on for six months.

Within the first two weeks post-CAR T-cell therapy, when your blood counts may be at their lowest, that's when we think about using a medication called Levaquin, as long as you're not allergic, to prevent any bacterial infections if your counts were very low and you were considered to be neutropenic, or have a very low neutrophil count.

For viral infections, we usually keep patients on antiviral prophylaxis for about 6 months after CAR T-cell therapy, typically acyclovir or valacyclovir. We don't usually take that off before the six-month period because we're waiting for some of the cells we know we depleted with lymphodepletion to repopulate your body. So usually, we keep either acyclovir or valacyclovir on for at least 6 months before we start checking the CD count or the lymphocyte count to make sure you have repopulation.

[22:06] You can start revaccinating as early as six months. That said, not every institution revaccinates, so practices vary a bit. Your institution might or might not. It's just going to depend on where you're being treated.

[22:30] Usually, within  the first 30 days is when we see the height of fungal infections. We may put you on something called fluconazole. Some institutions do it as prophylaxis, but many have moved away from it. It’s still pretty common.

After CAR T-cell therapy, you will be given medicine to protect against PJP pneumonia or pneumocystis pneumonia. We usually keep that on for that same six-month period because we want those lymphocytes to come back up.

[23:00] At the six-month mark, we may check something called the CD4 count, which shows whether a subset of your T-cells has repopulated your body.

If it's over a certain number, and most institutions have that magic number at 200, that's when we may peel off those prophylactic antimicrobials, so either the acyclovir, valacyclovir, Bactrim, or the trimethoprim-sulfamethoxazole.

[23:22] We usually start monitoring you for hypogammaglobulinemia at the 30-day mark. So, that could be when we're doing the IVIG replacement for you.

[23:35] Potential late side effects of CAR T-cell therapy include neurological and cognitive changes.

We look at whether you have decreased attention or memory problems. Are you processing information more slowly than usual? Do you have headaches or sleep disturbances?

[24:05] Less often, neuropathy occurs. Some patients experience hand tremors, so bringing a spoon to their mouth may be more difficult.

[24:14] We also look for mood changes. Mood changes are often caused by inflammation.

Sometimes we see this in patients who were in the ICU, or have had more steroids, anemia, or sleep disturbances.

[24:33] It's unusual to have long-term cardiac effects after CAR T-cell therapy.

If they occur, it's usually after severe cytokine release syndrome or a very prolonged ICU stay, and is due to inflammation.

[24:50] Some people are deconditioned after CAR T-cell therapy.

It’s very common for someone to become deconditioned after being hospitalized for a period of time. Your heart rate may be a little elevated compared to before. CAR T-cell therapy, because you're getting more active.

[25:09] We see reduced stamina that improves with physical activity.

There is a small risk of arrhythmia, usually due to a pre-existing condition.

For example, if you have atrial fibrillation and it’s been under good control, sometimes that inflammatory response with CAR T-cell therapy, and the fluid shifting a little bit, can trigger arrhythmia.

Very rarely, there may be side effects due to steroid use on your muscles, including your heart. Your heart is a big muscle. The data on that is really still evolving.

Symptom-triggered cardiac evaluation is sometimes recommended.

It's not routine to need a cardiologist after CAR T-cell therapy, but depending on what your course looks like, you may be referred to cardiology. This is very, very uncommon, but it is very, very manageable.

[26:17] Secondary cancers are cancers caused by prior cancer treatment. They're rare. A very small percentage of patients may get these.

T-cell malignancies are the ones we think of with CAR T-cell therapy, and again, are extremely rare.

A few years ago, the FDA issued an alert about this. But it remains very, very uncommon for us to see anything that is T-cell-driven.

Obviously, any new malignancy is very serious, but usually they’re very treatable.

Regular monitoring will help with early detection, as will reporting everything to your oncologist. If you see something, say something to them.

Report any unexplained fatigue, new weight loss, sweats, or new lumps, as these could be a little more T-cell driven.

[27:15] There can be late psychosocial effects, such as anxiety or depression, depending on how your course went. Some people have anxiety post- CAR T-cell therapy, especially if they had some significant side effects or trauma-related symptoms after ICU or hospitalization. Some people have a terrible fear of relapse, and that's totally understandable.

It’s really important that you talk to your oncologist or your nurse practitioner about any sexual health concerns, so that they can refer you to a specialist to help with that.

Relationships can strain after CAR T-cell therapy and cause caregiver distress. Depending on whether you received your CAR T-cell therapy in the outpatient setting or in the hospital,   there is going to be a little bit more caregiver burden in the outpatient setting.

[28:11] Financial toxicity can occur because these therapies are extremely expensive, as well as ongoing medical costs after CAR T-cell therapy.

[28:22] Risk factors for having late effects after CAR T-cell therapy include advanced age, having more comorbidities before CAR T-cell therapy, baseline performance status, and high disease burden. 

If you had problems like diabetes or heart complications going into CAR T-cell therapy, that would put you at a higher risk for having some of these late effects.

Baseline frailty or performance status. Performance status is how challenging or easy it is for you to do certain daily tasks.

A high disease burden can also increase your risk of late effects. Do you have a really big, bulky tumor? Have you had a prior transplant? Are there cytopenias – that baseline of how your marrow is functioning? If so, you might be at higher risk for low blood counts after CAR T-cell therapy.

Other factors include the severity of CRS and ICANS, whether you needed a hospital stay to treat them, the culmination of steroid and tocilizumab exposure, how often we had to intervene, and what your inflammatory markers were.

Obviously, a profound decrease in your B-cells is going to put you at a higher risk for infection.

[29:51] Self-monitoring for side effects.

Any sign of infection needs to be reported to your oncologist. So, fever, chills, new cough, shortness of breath, painful urination, and new sinus symptoms. If the symptoms are new, it's better to give your oncologist a quick call to make sure that it's nothing serious. They may want to bring you in for evaluation or testing.

Symptoms of low blood counts include bruising easily, having tiny red dots on your skin, and prolonged bleeding. If you have a cut on your hand, is it bleeding for a really long time? Do you have bleeding gums? Very severe fatigue or dizziness can also be a sign of low counts and anemia.

For neurologic effects and cognitive symptoms, we want your caregiver to report any new confusion, severe headaches, new weakness, and seizures. If you’re having a seizure, call 911 first and your oncologist afterward.

Also report significant memory problems, whether new or ongoing, and significant changes in the ability to focus or pay attention.

[31:13] Self-monitoring for heart and lung problems.

If you're having chest pain, palpitations, new shortness of breath, fainting, and leg swelling, those are all things to report, whether urgent or emergent.

[31:30] Other things that we want you to report are unintended weight loss, persistent night sweats, new night sweats, new lumps, or bone pain. We may want to do a workup for a secondary or new infection.

[31:35] When do you need emergency or same-day care? 

If you have a fever, always follow your CAR-T team's instructions. Not every fever is an emergency, but it may require urgent treatment. So always call your oncology team to ask them how they'd like to proceed with the fever.

Chest pain, shortness of breath, new neurologic deficits, seizure, and uncontrolled bleeding are always an emergency. Some of these may warrant you calling 911. Others may warrant a same-day visit with your oncologist, but definitely give them a call. If they've told you that for any of these symptoms, you should call 911, call 911.

[32:37] When to seek care within that 24 to 72 hour period, for me, is more urgent care, for a worsening cough, moderate shortness of breath, persistent vomiting or diarrhea, and the risk for dehydration. 

Any new significant bruising, worsening fatigue, or shingles-like rash, definitely give a call. Definitely give a call because they may want to see you.

[33:06] Mild but persistent fatigue, sleep issues, mood changes, and sexual health concerns are not talked about enough in survivorship care. There are specialists who can help you with these issues.

And we as medical professionals don't talk about it enough, so I just really want to impart any sexual health concerns. I want you to talk about it. There are definitely things that we can do and things that we can try.

Return to work and school challenges. Obviously, it's going to be a transition period after.

[33:50] So after CAR T-cell therapy, who should you call? Always call your CAR T-center or your oncologist team first, especially during the first year.

Obviously, if it's a true emergency, we want you to call 911, then call your CAR T center or oncologist.

But in general, for those non-emergent symptoms, call your CAR T-cell center because it could be a side effect of CAR T-cell therapy.

If your primary care clinician is coordinating with the CAR T team, you can also let them know. 

[34:17] Who should you contact when a referral is appropriate?

If you have persistent cognitive neurologic symptoms, you may need to see a neurologist or a cognitive rehab specialist. For persistent heart problems, you may need to see a cardiologist or a pulmonologist.

For depression, anxiety, or PTSD, it may be a mental health provider, a social worker, or a psychologist.

And then, for deconditioning, when you have that muscle weakness, you may see a physical or occupational therapist after CAR T-cell therapy.

[34:55] To manage the risk of infection, I can't say enough times, hand-washing, hand-washing, hand-washing, hand-washing. It is the easiest way to reduce your risk of infection.

Mask in high-risk settings when you're immunocompromised. You're not going to be as severely immunocompromised after CAR T-cell therapy as you are after a transplant. You may not need to do this as often or as much but definitely ask your provider if it's something you should be doing.

Think about food safety and not eating things that may make you sick.

[35:28] Definitely talk to your provider before you travel. Have a collaborative discussion with them about what that may look like for you and any preventive measures you may take before travel.

[35:41] Dental care and skin care reduce the portals of entry for infection. So do really, really good mouth care and really good skin care.

[35:51] Vaccination plan adherence once cleared by the treating team.

Every institution revaccinates differently. At my institution, we actually don't revaccinate.

At other institutions, they do an entire revaccination series, like you would after a transplant. And then some institutions land a little bit in the middle, where they'll do some vaccinations but not all.  So it's just going to depend on your institution's practice.

[36:17] You can improve functioning after CAR T-cell therapy by remaining physically active and gradually returning to aerobic and resistance activities to improve your fatigue, your stamina, your strength, and your mental health.

You can address deconditioning at the RCU. Get in with physical therapy or occupational therapy, and try cognitive rehab strategies as well.

[36:45] To improve sleep, establish a sleep routine.

Train your brain to use the bed only for sleep and sex. Limit alcohol, because alcohol will mess with your sleep, as will caffeine.

Decrease screen time before you go to bed, so you’re not on your phone, not watching TV, things like that.

Maybe just read an actual paper book.

[37:13] For mental health, screen for anxiety, depression, or PTSD. Cognitive behavioral therapy (CBT) or support groups may help

Exercising can also help your mental health.  And then caregiver support as well.

[37:30] Key takeaways: 

Most people feel better over time. CAR T-cell therapy is really, really well tolerated.

It can take weeks to months to get your strength back and return to your full functioning.

In general, people feel well after CAR T-cell therapy, and their quality of life will improve.

Some symptoms will linger. Talk to your oncologist about that and see if there's any intervention they can do to help you feel better..

Common side effects that can show up later after CAR T-cell therapy are low blood counts and a weak immune system that can lead to infections. There can be ongoing brain symptoms, such as trouble with memory or focus.

The risk factors for side effects include having a high disease burden or many prior cancer treatments before CAR T-cell therapy, having a large, bulky disease, and experiencing significant side effects during CAR T-cell therapy, such as fevers, severe inflammation, or confusion.

You should call your CAR T-cell team if you have a fever, unusual bleeding or bruising, new confusion, or trouble breathing.

A bunch of healthy habits can help you feel better, such as gentle exercise, getting good sleep, eating healthy foods, and managing stress.

And now we'll move on to questions.

Question and Answer Session

[40:01] Moderator: Thank you, Ms. Ramsdell, for this very informative presentation.

We have one question that I'm going to start with: I am a Carvykti CAR T-cell patient from November 2025. I am still experiencing side effects, Bell's palsy, muscle weakness, and GI colitis. How much longer would you predict these will continue? What can I do to resolve them?

[40:52] Linda Ramsdell: That's a great question. And I'm so sorry that you're feeling so poorly.

So Bell's palsy can happen after CAR, T-cell therapy and it's something that we see sometimes with the Carvykti product or cilta-cel, as well as GI colitis.

The way patients recover from both of those things varies, depending on their bodies and how they respond to the treatments.

It sounds like you've been having these symptoms for quite some time. I would recommend, if you haven't already seen a specialist, - a neurologist or a gastroenterologist - that you should probably connect with one. There are many ways we can treat these problems, particularly GI colitis and ongoing Bell's palsy. So, I would recommend seeing specialists for those.

[41:55] Moderator:Can CAR T-cell treatment have an impact on your dental health?

[42:05] Linda Ramsdell: It does not usually. I know that with bone marrow transplants, you must do really robust oral care and be really careful about your dentition, but we don't have the same side effect after CAR T-cell therapy.

We do recommend good oral hygiene because your mouth can be a portal for infection. We don't want you to get any sort of mouth infection while your counts are low. 

[42:39] Moderator:How can we find cognitive behavioral therapy (CBT) groups or therapists?

[42:44] Linda Ramsdell: A lot of times, your insurance will be able to help determine who within your plan, is either a CBT therapist or just a general therapist.

If not, I would recommend reaching out to the CAR-T Center, They may be able to connect you with social work to either see you as a therapist or put you in touch with someone who specializes in oncology.

[43:12] Moderator: I would like to add that BMT InfoNet does have a directory of mental health providers. So, if you do need to go outside your center, visit bmtinfonet.org to find a directory of mental health providers. They are vetted to ensure they know about CAR T-cell therapy.

You can search by the state you're in to see if there is a provider who knows about CAR T-cell therapy, understands the long-term effects, and is very willing and able to treat you.

We also have an online support group for CAR T-cell therapy recipients. You can learn more by visiting our website at bmtinfonet.org and checking out the events tab.

[44:33] Moderator: Would you recommend probiotics for GI colitis post-CAR T treatment?

[44:40] Linda Ramsdell: That's a great question, and it's actually more controversial than you think.

The best answer is to listen to your oncologist. We have seen in certain settings that using probiotics in immunocompromised patients can actually increase the risk of infection.

I don't know if that would be the case for you. It's a really interesting question,  given that there's a little bit of a divide there.

I think that if you're thinking about GI colitis, you may be more likely to have leaky gut, which could increase your infection risk, but definitely have that discussion with your oncologist, as they'll be able to direct you best. They're going to know what therapy you're on and what your individual risks are.

[45:35] Lynne Spina: You mentioned in your presentation about the lack of sexual health discussions with providers. This person is asking, are there projects or initiatives to increase awareness of sexual health issues after CAR T? Are there better resources for us?

[45:51] Linda Ramsdell: We have the beginnings of them, yes. So, there are now survivorship clinics that will automatically plug you in.

I hope more providers in the field are starting to talk about these post-effects with their patients, but I think we can still do a much better job than we're doing.

It's really with the survivorship clinics that we're seeing this increase in having these discussions and really getting all patients the help that they need to return to their true baseline and engage in some of that activity that would really make them feel a little bit more like they were before CAR T, which is really important.

Moderator: I would also like to mention to everyone that on Wednesday at 7 p.m. Eastern time, we will have a presentation on sexual health after CAR T and transplant. So join us then.

[47:01] Moderator:I'm still getting Granix shots after almost one year of post-CAR T. My platelets are borderline, and so are my neutrophils. Is it uncommon for this amount of time?

[47:22] Linda Ramsdell: It is possible that this is uncommon. It would depend on why your provider thinks you need those shots and why you are having those low platelets at this time.

Sometimes, depending on where your bone marrow function was before CAR T-cell therapy, it may be a little bit closer to your baseline, and other treatments may be causing that.

I think that it is prolonged, but it may or may not be abnormal.

[48:08] Moderator: If you have a CAR T-cell therapy for multiple myeloma, is that any different than if you have a different disease like lymphoma?

[48:21] Linda Ramsdell:  What we see for lymphoma CARs and for multiple myeloma CARs during the acute toxicity phase are actually very different.

So, with lymphoma, we're going to see, with some products, potentially more robust cytokine release syndrome and neurologic toxicity than we see with some of the multiple myeloma products.

The timelines are very interesting, too. For one of the multiple myeloma products, all immediate post-CAR T toxicity occurs on days 1 and 2. With the other product that we give, everything happens on days 7 and 8.

We typically see higher grade CRS with the lymphoma products, although there is one where we usually see up to grade two, which is fever and a little bit of low blood pressure, low oxygen. And it just kind of stays right there.

Knowing which product you're getting will let you know which side effects to expect, when, and how much.

All of the products we give are different. Some patients feel kind of crappy earlier on and not so great. They'll feel good for a week, then start to feel the side effects.

[50:06] Moderator:I have a basal cell carcinoma eight months after my second CAR T and three years after my first CAR T. Is it likely a secondary cancer, or is it a result of ordinary aging?

[50:15] Linda Ramsdell: I would say it is likely due to aging.

When we talked about secondary malignancies after CAR T-cell therapy, I was referring  to T-cell lymphomas, myelodysplastic syndromes (MDS), or acute myeloid leukemia (AML).

It's a very interesting question. I think it would depend on what they thought the origin was, but it's actually pretty common with advancing age.

[50:45] Moderator: Whom should they talk to about this?

[50:53] Linda Ramsdell: I would talk to your CAR-T oncologist if you can. I suspect they wouldn't consider it secondary, but again, it depends on what your oncologist says. I'm only speculating.

[51:21] Moderator: This person is wondering about the issue of caregivers. How long is it advantageous to have a caregiver after CAR T-cell therapy?

[51:37] Linda Ramsdell: That's a great question. And I don't think it's as straightforward an answer as you may think.

So, your CAR T institution will mandate that you have a caregiver for a period of time. At my institution, it is a minimum of 14 days that you have to have a caregiver. We actually extend that out depending on if you have the neurologic side effects.

So, it's a minimum of 14 days depending on the product. But how you feel and how long you feel you need them is important, because every patient recovers differently.

If you're having really significant fatigue after CAR T-cell therapy,  you're going to need that caregiver for longer.

We have some patients who really feel a bit knocked down after CAR T-cell therapy. And we have other outpatient patients who are walking one or two miles to get to us every single day. So, it's really going to depend on how you're feeling post-CAR T.

[52:46] Moderator: So we are done with our Q&A now. 

I'd like to thank Ms. Ramsdell for a very helpful presentation.

And thank you, audience. You had excellent questions.