Tag Archive for: cytokine release syndrome

Expert Perspective | How Bispecific Antibody Therapy is Transforming Myeloma Care

 How has bispecific antibody therapy changed myeloma care? Tiffany Richards, a myeloma nurse practitioner, explains how bispecific antibody therapy works, who this therapy may be right for, and the important role of the care partner when caring for a loved one. 

Tiffany Richards, PhD, APRN-BC, AOCNP is a Nurse Practitioner in the department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center.

See More from The Care Partner Toolkit: Bispecific Antibodies

Related Resources:

Proactive Steps for Supporting Your Loved One Through Bispecific Antibody Therapy

Proactive Steps for Supporting Your Loved One Through Bispecific Antibody Therapy

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

Care Partners | Tools for Self-Care and Managing Emotions

Care Partners | Tools for Self-Care and Managing Emotions

Transcript:

Katherine Banwell:

I’d like to start by learning a bit about you. Can you tell us about your role in the Myeloma Care Team? 

Tiffany Richards:

Yes. So, I’m a nurse practitioner and I’ve been here at MD Anderson for 20 years working with patients with plasma cell dyscrasia. And so, I work in collaboration with our nurse as well as our myeloma physician to not only evaluate patients, what their responses are to treatment but also to make sure that they’re tolerating treatment well, and then adjusting medication or providing supportive medications so that patients are better able to tolerate their therapies.  

Katherine Banwell:

Bispecific antibody therapy is a newer therapy. How has this option changed myeloma care?  

Tiffany Richards:

Between that and CAR T, it’s really offered our patients the opportunity to utilize the body’s own immune system to help fight the myeloma cells. I think the one nice thing that the bispecific antibodies have allowed is that you’ve had a group of patients that maybe weren’t candidates at that time for CAR T either due to other medical conditions or maybe because their disease isn’t at a place where we would be able to get them to CAR T.   

Either maybe their lymphocyte count was low, white blood cells, and so maybe the ability to collect those T cells would be impaired or the disease itself was rapidly progressing and so the patient would not be able to be off therapy in order to have those T cells collected.  

And so, the bispecific antibody allows us to utilize those T cells to go after the myeloma cells without having to go through the process of having to collect those T cells. And so, that has really changed for that group of patients. But also, we have a bispecific antibody therapy that doesn’t target the same receptor that the CAR T-cell therapies do. So, our CAR T-cell therapies target something called BCMA, which stands for B Cell Maturation Antigen.

That’s expressed on the surface of the myeloma cells, and there’s a bispecific that targets a different receptor called GPRC5D. It’s a lot of letters. But it’s a different target, and so even for patients who have had CAR T-cell therapy we can use that bispecific antibody now for those patients who have maybe progressed on CAR T.  And so, it’s allowed another treatment option for patients that they didn’t otherwise have.  

Katherine Banwell:

So, how many bispecific antibody therapies are available for people and how do they differ? 

Tiffany Richards:

So, we have three. So, we have two that target the BCMA; so, that would be teclistamab (Tecvayli) and elranatamab (Elrexfio). And then, we have a third one that targets the GPRC5D which is called talquetamab (Talvey). And so, we utilize the talquetamab if we wanna use a bispecific therapy that does not target the BCMA. And then, for patients who maybe wouldn’t be able to get to CAR T, we might use one of the BCMA therapies.  

And as far as differences between to the two BCMA, really, they’re pretty similar as far as response rates. They haven’t been compared head-to-head. And so, different centers might utilize one versus the other depending on what they have on formulary. So, I would just say, whatever one your center is utilizing that would be the one to go with. 

Katherine Banwell:

Why is a care partner required for patients who are undergoing bispecific antibody therapy?  

Tiffany Richards:

That’s a great question. So, it’s because of some of the side effects that we can see in patients who are undergoing bispecifics. So, similar to CAR T cell therapy, we can see what’s called cytokine release syndrome. We abbreviate that by CRS. And then, we also can see neurotoxicity. We don’t see it to the same degree that we see it with CAR T but patients can still experience it.  

So, cytokine release syndrome, you can get fevers. You can have a drop in the blood pressure, chills, increase in the heart rate. And so, because of that you have to be monitored closely because, if you would start to have cytokine release syndrome, we need to make sure that we’re properly intervening and we can utilize a different medication called tocilizumab (Actemra) to help quiet the immune system a little bit, quiet down those T cells. And so, you need to have somebody that’s with you at all times that knows you, and also, same with the neurotoxicity. Again, we don’t see it to this same degree that we see it with CAR T, but that doesn’t mean that it can’t happen.  

And so, you really need to have that care partner alongside of you. Plus, I think just with these immune therapies, it’s a lot of information that we’re giving patients.   

And so, it’s important to have that other person there to kind of hear what maybe you’re not able to catch. There’s a lot of information that’s being given to you and can be very overwhelming at times. And so, it’s important to have that second person there to kind of be another set of ears as you’re going through this journey. 

The CAR T-Cell Therapy Process | How Care Partners Play a Role in Each Step

 What happens during CAR T-Cell therapy process? Dr. Adriana Rossi, a myeloma specialist, walks through each part of the process and the role that care partners play in each step, emphasizing the importance of communication with the healthcare team.

Dr. Adriana Rossi is Director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.

Download Resource Guide

See More from The Care Partner Toolkit: CAR T-Cell Therapy

Related Resources:

Advice for Myeloma Care Partners | Monitoring for CAR T-Cell Therapy Side Effects

Advice for Myeloma Care Partners | Monitoring for CAR T-Cell Therapy Side Effects

Understanding Your Role as a CAR T-Cell Therapy Care Partner

Understanding Your Role as a CAR T-Cell Therapy Care Partner

CAR T-Cell Therapy | Monitoring for Side Effects As a Care Partner

CAR T-Cell Therapy | Monitoring for Side Effects As a Care Partner 

Transcript:

Jamie Forward:  

Now we’re going to sort of walk through the steps of the CAR T process and what happens in each step, and how the care partner can support the patient during this time. So first, is there a consultation once a patient has been approved for this therapy? 

Dr. Adriana Rossi:  

Absolutely. There are several consultations. The first one, once the patient’s identified by a referring physician, they will come and meet with myself and again, the coordinators and several members of that team to make sure that it seems like a good fit. That this is the right time, and identify any steps that we can take to really set that patient up for success.  

Jamie Forward:  

Okay. And, how can the care partner participate in this meeting? Are there key questions they should be asking? 

Dr. Adriana Rossi:  

Absolutely. Again, this is the beginning of the journey, and they should absolutely be there. Mostly because a lot of the information, this may be the first time they’re hearing again, the words. The concepts. The timeline. So, do ask about when things are going to be happening. As the CAR T physician, I do this all day. So, it’s very clear in my mind, but until it’s clear for them, again, ask more questions. Ask for clarification. 

Be clear on what resources are available. If there’s something that there is a question like transportation, or sequential appointments, or children in the family. All kinds of things. Really be as curious and as vocal as you’re up for.  

Jamie Forward:  

Right. Arranging for childcare and pet care is probably really important during this time. 

Dr. Adriana Rossi:  

Exactly. 

Jamie Forward:  

What about financial planning? Is that a good time to ask about insurance and who to coordinate with there? 

Dr. Adriana Rossi:  

Absolutely. Again, you will meet with social work. But, if there are specific issues that we’ve already identified, specific resources, specific paperwork, we can get that started right away.  

Jamie Forward:  

Okay. Great. So then, after that, once all of that has been squared away and you’re ready to go into the CAR T-cell therapy process, there’s the T-cell collection, correct? 

Dr. Adriana Rossi:  

So again, to distinguish it from stem cells, I think it’s important to know it is a one-day collection for CAR T. 

There are no injections or other preparations ahead of time. There’s no minimum number of cells that we’re aiming to get. It really is a one-day commitment to collect the cells that we collect, because they’ll be then engineered and modified before they’re ready. And so, it’s not the ordeal that sometimes you have to go through for stem cells.  

Jamie Forward:  

Okay. So, the care partner should just be there during that time to be a supportive loved one. 

Dr. Adriana Rossi:  

Exactly. And, it can be a long day. You’re tethered to the machine for a few hours. And, when all goes well, it is an exceedingly boring experience. So, be entertaining and be nearby. Always helpful.  

Jamie Forward:  

That’s great advice. So, once the cells have been collected, can you walk through the next steps? I believe there are bridging treatments involved. Are those administered inpatient or outpatient? 

Dr. Adriana Rossi:  

Absolutely. Bridging therapy is the therapy the patient receives while the cells are out being manufactured. And really, the goal there is not to get rid of myeloma. It’s just to prevent it from growing. Because myeloma that is not cared for tends to grow quite quickly. There are options to do it inpatient. To do it outpatient. There are certain therapies that would require the patients come to our center. Others that are easily given with their local oncologist. So, we really try to find something that the myeloma will be sensitive to, and that will hopefully not be too toxic, so there’s not a big recovery or a big downtime as we are preparing for the hospital stay for CAR T. 

Jamie Forward:  

Okay. And, how can care partners support the patient at home during this time? I would imagine it’s sort of an anxious time. 

Dr. Adriana Rossi:  

Absolutely. Many times, the bridging is something that may be familiar. Like, we’re recycling drugs they’ve seen before.   

But, these could be brand new drugs. And, I think every time you’re experiencing a new cocktail, there is some learning of how will you react, and the anxiety that can come with that, as well. There are a few times when there are delays in the cells getting ready. So, it’s not a very exact day, and that waiting period, wondering will they really come on the day they’re expected absolutely could be an anxious time. I think keeping each other company and just actively working to be your healthiest self for whenever the CAR T is ready, and knowing that working with your physicians, we are all working behind the scenes to work to the greater success hopefully is helpful.   

Jamie Forward:  

And then, finally in the process, the cells are infused back into the patient. Since this is a critical time for patients, how can care partners best be prepared to help their loved one?  

Dr. Adriana Rossi:  

One of the most common side effects is something called CRS. 

Which patients experience as a fever. And, I think many times in blood cancers, we really worry about fevers, because those could be infections. I think it’s important to be prepared and expect the fever so that again, it’s not oh no, what is this? We were waiting for it. It tends to come at a very scheduled time dependent on the product. So, just reassuring. Remembering yes, there are toxicities, but they are expected. Plan for them.

The medical team will have an antidote. We’ll have steps that we take depending on what comes up. And, the reason for being in the hospital is exactly to allow the medical team to respond very quickly. Most of the time, very little happens, and that is wonderful. So, if anyone is feeling bored, that is great. Celebrate it with them. No news is good news during the couple weeks in the hospital.  

Jamie Forward:  

Okay. And, how long is the patient monitored for side effects in the hospital following new infusion?  

Dr. Adriana Rossi:  

So, depends on the product. Ide-cel tends to have very early reactions. And so, our policy is one week for ide-cel (Abecma) and two weeks for cilta-cel (Carvykti) because there, most of the side effects are around seven days in. So, we wait for the inflammation to peak and resolve. And, once it’s safe, we aim to get patients home. But, once they leave the hospital, they should for at least a few weeks be very close to the CAR T center, and usually require two to three visits a week for that close monitoring. 

Advances in CAR T-Cell Therapy Side Effect Management

Are there new ways to manage the potential side effects of CAR T-cell therapy? Dr. Rahul Banerjee, a myeloma specialist and researcher, reviews common side effects of this treatment option and discusses new ways that providers are approaching the management of both short-term and long-term issues. 

Dr. Rahul Banerjee is a physician and researcher specializing in multiple myeloma and an assistant professor in the Clinical Research Division at the University of Washington Fred Hutchinson Cancer Center in Seattle, WA. Learn more about Dr. Banerjee.

Download Resource Guide

Related Resources:

CAR T-Cell Therapy for Myeloma | Challenges and Unmet Needs

CAR T-Cell Therapy for Myeloma | Challenges and Unmet Needs

Myeloma Research | Updates in CAR T-Cell Therapy

Myeloma Research | Updates in CAR T-Cell Therapy

How Long Is CAR T-Cell Therapy Effective in Myeloma? An Expert Explains

How Long Is CAR T-Cell Therapy Effective in Myeloma? An Expert Explains

Transcript:

Katherine Banwell:

Well, let’s talk about side effects of CAR T-cell therapy. What advances are being made in managing them?  

Dr. Rahul Banerjee:

Excellent question. So, I break the toxicities into short-term and long-term toxicity of CAR T therapy.  

And this is actually fairly similar for both, regardless of the underlying disease, whereas lymphoma, leukemia, or myeloma, very similar. Just so everyone, just to reorient the audience, short-term toxicities, people often talk about the big two. I’m going to say the big three, actually. The first one is cytokine release syndrome, or CRS, which is inflammation, typically causing fever, sometimes low blood pressure. 

The second is neurotoxicity, or ICANS. For reasons that aren’t entirely understood, sometimes all those chemicals from inflammation can cause people to feel a bit off mentally or cognitively. Sometimes people might not be able to talk, or might not talk correctly, or sometimes have issues along those lines. 

And the third, I would say, is low blood counts or infections. Both the lymphoma, leukemia CAR Ts and the myeloma CAR Ts very rapidly deplete the good plasma cells or the good lymphocytes, the good cells in the bone marrow, and so immediately you see patients at risk of infections. 

And for a complicated number of reasons, one of which being cytokine release syndrome, CRS inflammation within the bone marrow, where all these cancer cells are hiding, the stem cells in the bone marrow hide away, right? They kind of go into a bunker to stay away from all of this. And so patients often have low blood counts for significant amounts of time after CAR T therapy, something called hematotoxicity. 

Those are short-term toxicities. Long-term, very briefly, that risk of infection and low blood counts is still there, I would say, for up to a year after CAR T therapy, sometimes longer for some patients. There is a risk, obviously, of the original cancer coming back, in this case the myeloma, particularly myeloma. 

And three, there are rare delayed toxicities to be on the lookout for. So, one of them, for example, with cilta-cel or Carvykti, the numbers are hard to see what the rate is prospectively because it’s been going down with time.  

But rarely, I would truly in my heart say 1 percent of the time, if not less, patients can get Parkinsonism, where they’re not able to move as rapidly, they’re not able to, they’re kind of shuffling gait, having tremors, et cetera. Not the same as normal Parkinson’s disease, because the normal meds don’t work, just time is often the only thing that really makes a big difference. 

Technically, there’s a box warning on all CAR T therapies now about a risk of second cancers. That risk is not new to anyone who’s ever received any treatment for myeloma because from the very beginning, we tell people that these drugs have been linked to a potential risk of second cancers in the future.  

In terms of strides that are being made to improve that, I think we’re making a lot of improvement. So, I think the biggest thing that we’ve learned, and I remember when I was a trainee, for example, when I was in my medical training, the early days of CAR T therapy – actually out in Philadelphia, I trained at Penn – and there, we were scared about trying to tone down the inflammation.  

When these side effects happen in the short term, the goal is if the patient’s obviously having side effects, and the question is, “Can we not kill the T cells? Can we just dial that down?” Say, “Look, I’m happy the T cells are angry. I’m happy they’re killing the cancer, the myeloma in this case. But can you just dial it down a little bit with a medication called tocilizumab (Actemra), or corticosteroids like dex?” 

We used to be very nervous about doing that because we said, look, the patient’s put all this blood, soil, sweat, and tears right into this CAR T therapy, and we don’t want to do anything that can hinder the T cells from working.  

Now we know that that level of inflammation is not doing anyone any favors at all, and so we’re able to really start these medications to just dial down the immune system faster. As soon as someone has a fever, for example, at many centers, we do consider, within an hour or two, giving one of those medications. Don’t wait till they’re in the ICU, give it then.  So, I think just tweaking our algorithms has made probably the biggest difference, in my mind, to make CAR T safer.  

Other things that have helped, I think, are better understanding of why patients have these other toxicities and strategies to prevent it. And so, for example, the neurotoxicity risk, some of it is part of disease burden. We think that patients who have a lot of disease going into CAR T therapy may have more toxicities. So, giving better treatments as, quote-unquote, “bridging treatment” before CAR T therapy that we have better, newer treatments now, have sometimes helped to really debulk the disease before going to CAR T.  

That’s helped a lot with side effect management. In terms of long-term risk, the third thing that I really encourage all my patients and all my oncologist partners in the community to really push for is the infection risk and how do we prevent it? So, I think probably the biggest thing that we’ve recognized is intravenous immunoglobulin, which is IVIg, which is basically an antibody transfusion.  

When people donate blood, they also donate plasma, often, and the plasma contains antibodies against whatever they themselves have fought off circulating in the area – viruses, colds, et cetera. 

You can take all those antibodies, put them all together into a sterile bag, and give it to the patient who’s gotten CAR T therapy. Because the patient’s gotten CAR T therapy, assuming it’s working, which it normally does for several months, right, to knock out all cells, good and bad immune cells, that patient is not making any antibodies at all. They’re a sitting duck for infections. And so I would say IVIg, using that routinely now is not just the exception once they’re having infections, but even in the absence of infections, just giving it.  

Insurance companies are not happy with me when I suggest that because it’s expensive, but that’s the right thing to do for patients, and I think that has helped a lot, in my experience, for all of these immunotherapies, both CAR T and bispecific antibodies, to lower the risk of infections. 

Proactive Steps for Supporting Your Loved One Through Bispecific Antibody Therapy

How can you best care for a loved one who is undergoing bispecific antibody therapy? Dr. Craig Cole, a myeloma specialist, provides key advice for care partners emphasizing the necessity of taking notes and for having a solid plan if issues arise, and he shares key questions to ask the doctor about bispecific antibody therapy.

Dr. Craig Cole is a multiple myeloma specialist at Karmanos Cancer Institute in Detroit, MI and in East Lansing, MI. Dr. Cole also serves as an associate professor at Wayne State University and at Michigan State University. Learn more about Dr. Craig Cole

See More from The Care Partner Toolkit: Bispecific Antibodies

Related Resources:

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

Essential Monitoring Following Bispecific Antibody Therapy for Myeloma

Essential Monitoring Following Bispecific Antibody Therapy for Myeloma

Being Empowered | Why Care Partner Should Feel Comfortable Voicing Concerns

Being Empowered | Why Care Partner Should Feel Comfortable Voicing Concerns

Transcript:

Katherine Banwell:

Dr. Cole, what sort of questions should care partners be asking the care team when a loved one is undergoing bispecific antibody therapy? 

Dr. Craig Cole:

I think one of the big questions and – oh first I would say write everything down. Write everything down and have your care provider write things down or record them. Because I think it’s important to have that – have something written on hand. In our house we put everything on the – instructions on refrigerator with a magnet to make sure everyone sees it. But the one – one big question to ask is, “What are the – with this specific antibody that the patient’s receiving, what is the risk of the of the cytokine release syndrome?  

What’s the risk of the neurotoxicity that we talked about in the timeline?” Because those can be very different. “When should I worry? And how long should I be watching for these side effects?” The other thing is to have a solid plan of what to do if there are – if there’s any side effects. And so frequently that doctors or providers will write a prescription for steroids or Tylenol to take if any of those symptoms happen, but also to have a phone number to call a provider or to call the clinic if something were to change. Because again, these aren’t symptoms that you want to sit on where you say, “Oh, I have a fever, no big deal.” I mean it’s definitely good to call, and so, having a plan set. And I would make sure that you have that written down and then talk back, repeat back to the doctor or the provider that the plan is set.  

It’s not a forever plan. It’s just doing those first few doses of the bispecific. And also knowing sort of – I think a really good question is knowing the long-term efficacy of these. I mean these therapies are – work really, really well, but also knowing what are the chances of this working, of it not working? And I always like to have a plan B. “If this doesn’t work well, what are we going to do next?” And I think that’s a very fair question to providers. 

Katherine Banwell:

Dr. Cole, is there anything else you’d like to add about caring for someone who’s being treated with bispecifics? 

Dr. Craig Cole:

I think that the biggest thing is how incredibly exciting these medications are. I mean, there are – I went through and talked about a lot of the bispecifics for cancer, but there have been revolutionary biospecifics for macular edema, for hemophilia, the bleeding disorder. And these are revolutionary drugs in cancer. And really, it’s incredible that – how well these drugs fight cancer. And the fact that they use your own immune system, not someone else’s immune system, not some chemotherapy, but using your own immune system is incredible. And so, I always tell people to be really encouraged that the technology is this – if you’d have asked me this 10 years ago about a bispecific antibody I would say that’s impossible.  

And now we’re at the cusp of that. And the other thing is to be involved in clinical trials, that all these, a lot of – there are a lot of clinical trials and bispecifics because it is the big, exciting thing. And so, if you have the opportunity to participate in a bispecific clinical trial, I would definitely encourage that because it really is the cutting edge of medicine these days.  

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

 
Dr. Craig Cole reviews the side effects of bispecific antibody therapy, the symptom care partners should be monitoring for, and the importance and impact of early intervention if any issues arise.

Dr. Craig Cole is a multiple myeloma specialist at Karmanos Cancer Institute in Detroit, MI and in East Lansing, MI. Dr. Cole also serves as an associate professor at Wayne State University and at Michigan State University. Learn more about Dr. Craig Cole

See More from The Care Partner Toolkit: Bispecific Antibodies

Related Resources:

Myeloma Care Partners | Understanding Bispecific Antibody Therapy

Myeloma Care Partners | Understanding Bispecific Antibody Therapy

Essential Monitoring Following Bispecific Antibody Therapy for Myeloma

Essential Monitoring Following Bispecific Antibody Therapy for Myeloma

Proactive Steps for Supporting Your Loved One Through Bispecific Antibody Therapy

Proactive Steps for Supporting Your Loved One Through Bispecific Antibody Therapy

Transcript:

Katherine Banwell:

Do side effects vary from patient to patient? 

Dr. Craig Cole:

Yes, so they actually vary greatly from patient to patient and from drug to drug. There’s some bispecifics for some cancers that have low risks of cytokine release so low that they don’t even need to come to the hospital. And some of them have such a high risk of those cytokine release syndromes that people are in the hospital for a few days.  

The other thing is usually the more tumor someone has, the more disease and cancer they have, the higher those risks of cytokine release. And so, it does vary from patient to patient to and from medication to medication. 

Katherine Banwell:

What should care partners understand about caring for someone during therapy? 

Dr. Craig Cole:

One of the big things that care partners should look for or to be aware of are – is the timeline for a lot of those symptoms. The highest risk for the side effects, the things to look out for, the neurologic toxicity, the fevers, and shortness of breath, and things are in the first few days of each dose of receiving therapy.  

Some of those therapies actually because of the neurotoxicity, they don’t let anyone drive, any patients drive for the first few weeks after receiving a bispecific. So, knowing the timeline, that in those first few days, that you really have to check the temperature, have a plan, know who to call, watch for those symptoms. But as the weeks move on, like after the second dose, there’s much less toxicity, third dose, even less risk. Fourth dose and on is very rare to have any of those toxicities, and so then you can relax. And usually people are able to drive. So being aware of the timeline’s important. 

Katherine Banwell:

Yeah. Are there advances being made in the management of side effects for bispecifics? 

Dr. Craig Cole:

Oh yes, and so that’s the – that’s one of the really exciting things is the – is what I was just talking to one of our trainees about this, about the evolution of the bispecific antibodies have been to make them more effective, make them more sticky, make them engage those T cells more while decreasing the toxicities. 

And so the ones that we’re seeing that are in clinical trials now that hopefully will be approved soon have less of those side effects, less hospitalization, and actually have a longer frequency of being given. The other thing is that we’re really beginning to learn a lot about treating cytokine release syndrome, especially as severe cytokine release syndrome. So, there was a drug that was used to treat severe COVID called tocilizumab (Actemra).  

Katherine Banwell:

Yeah.  

Dr. Craig Cole:

And that was used when people came in with COVID symptoms which can be a lot like cytokine release. The would receive this medication to help control that. Now we’re using that to treat cytokine release syndrome.  

And there’s quite a bit of data, especially in multiple myeloma in using it prophylactically to prevent cytokine release syndrome. And there are studies that show that the usual rate in multiple myeloma, kind of the specialty that I have, the usual rate of cytokine release – some cytokine release is about 70 percent with using prophylactic tocilizumab, which is just an antibody against one of those cytokines, IL-6. It goes down to – up to about 25 percent, so 75 to 25.  

And really it has no adverse side effects and doesn’t do anything with the outcome or the effectiveness of the bispecific antibodies.  

Katherine Banwell:

Well, that’s an incredible difference, isn’t it? 

Dr. Craig Cole:

Yes, yes, that was really – the trick is trying to get insurance companies to approve it and to get hospital systems to approve it.  

But I am very confident that very soon as we get more data about using it prophylactically that they’ll be incorporating it into the guidelines. 

Essential Monitoring Following Bispecific Antibody Therapy for Myeloma

Why is a care partner essential for someone undergoing bispecific antibody therapy for myeloma? Dr. Craig Cole, a myeloma specialist, discusses the essential role of care partners following treatment, emphasizing the importance of monitoring for potential side effects. 

Dr. Craig Cole is a multiple myeloma specialist at Karmanos Cancer Institute in Detroit, MI and in East Lansing, MI. Dr. Cole also serves as an associate professor at Wayne State University and at Michigan State University. Learn more about Dr. Craig Cole

See More from The Care Partner Toolkit: Bispecific Antibodies

Related Resources:

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

What Myeloma Care Partners Should Know About Bispecific Antibody Side Effects

Being Empowered | Why Care Partner Should Feel Comfortable Voicing Concerns

Being Empowered | Why Care Partner Should Feel Comfortable Voicing Concerns

Bispecific Antibody Therapy | The Important Role of Care Partners

Bispecific Antibody Therapy | The Important Role of Care Partners 

Transcript:

Katherine Banwell:

What is the role of a care partner for someone undergoing bispecific antibody therapy? 

Dr. Craig Cole:

Yeah, the care partner is, I think, a critical component of someone receiving bispecific therapy. And their reason is really to do with the side effects and monitoring the side effects of the therapy. What’s the big side effect of the bispecific antibodies is again when those T cells engage the cancer cells and they find the cancer, they release chemicals to destroy the cancer immediately.  

And those chemicals are from the T cells, can cause people to feel very ill, or can cause them to feel very ill very quickly, or they can have fevers, and they can have difficulty breathing. And that’s called cytokine release syndrome. Cytokines are the chemicals that the T cells are using to kill the cancer cells.  

Release, meaning that T cells are releasing that, and syndrome mean that different things can happen to different people. And the highest risk for the cytokine release syndrome is usually within the first two to three treatments, usually in the first two or three days of the therapy. And a lot of times when people get the bispecific antibodies, sometimes it’s given in a brief hospitalization like an overnight hospitalization, but then they go home.

And then the trick is monitoring for that cytokine release syndrome, the fevers that can be associated with that, shortness of breath, low blood pressure. And in having a couple people observing, watching for those signs and symptoms are really important. Because if cytokine release syndrome isn’t addressed immediately, it can progress to worse outcomes, meaning that the blood pressure gets lower, the difficulty in breathing gets worse.  

If let completely go, people can end up in the intensive care unit which is very, very, very rare. But that’s why we address this as early as possible. The other side effect, and probably kind of the most subtle thing, are some of the neurologic things that can happen with the bispecific antibodies. So, it’s the neurologic toxicity, or some people call it ICANS. And that’s when some of those cytokines that we talked about that are from the T cells can cross the blood brain barrier and cause patients to be confused.  

They can have word finding difficulties. They can feel – almost have stroke-like symptoms. They’re temporary, but they definitely need to be addressed. And sometimes patients may not be aware that they can’t find the right word, or they want to speak, and the words don’t come out, or when they speak it’s the wrong words are coming out.  

And that’s a real, real big sign that you need to call your doctor immediately, or your provider immediately if you have those neurologic symptoms. So, watching for those side effects, so low blood pressure, the high fevers, and stroke like symptoms. It’s not a stroke, but it’s just those chemicals in the brain that can cause people to have some neurologic problems. And again, if you address those immediately, they are definitely reversible.  

Myeloma Care Partners | How Can You Support Your Loved One During CAR T-Cell Therapy?

How can care partners be informed and prepared when a loved one is undergoing CAR T-cell therapy? Myeloma expert Dr. Adriana Rossi explains the role of the care partner in each step of the CAR T process, how to understand and monitor for side effects, and shares key advice for self-compassion and self-care when serving as a care partner for a loved one. 

Dr. Adriana Rossi is Director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.

Download Resource Guide

See More from The Care Partner Toolkit: CAR T-Cell Therapy

Related Resources:

CAR T-Cell Therapy | Monitoring for Side Effects As a Care Partner

CAR T-Cell Therapy | Monitoring for Side Effects As a Care Partner

An Essential CAR T-Cell Therapy Team Member | The Care Partner

An Essential CAR T-Cell Therapy Team Member | The Care Partner

Where Can Myeloma Care Partners Find Out More About Financial Support?

Where Can Myeloma Care Partners Find Out More About Financial Support?

Transcript:

Jamie Forward:

Hello and welcome. I’m Jamie Forward. Today’s program is part of the Patient Empowerment Network’s Care Partner Toolkit Series focusing on the role of the care partner when a loved one is undergoing CAR T-cell therapy.   

Today, we’re joined by a myeloma specialist who works with patients and their care partners. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team about what might be best for you. Let’s meet our guest today. 

Joining us is Dr. Adriana Rossi. Dr. Rossi, welcome. Can you please introduce yourself?   

Dr. Adriana Rossi:

Yes. Nice to be with you today. I am the director of the CAR T and Stem Cell Clinical Program at Mt. Sinai in New York.  

Jamie Forward:

Thank you so much. We’re glad to have you with us. Dr. Rossi, before we get into the role of care partners and the CAR T process, let’s talk about what CAR T-cell therapy is. Can you please give an overview of CAR T and how it works to treat myeloma?  

Dr. Adriana Rossi:

Absolutely. CAR T are genetically engineered cells. So, we generally use the patient’s own T cells, modify them to make them special killers just for that patient’s myeloma. And then, infuse them back into the patient over a process that I’m happy to go into in much more detail.  

Jamie Forward:

Sure. And, we’ll cover the process a bit later in the program. So, we can walk through that in just a bit. So, where does CAR T-cell fit into a myeloma treatment plan? 

Dr. Adriana Rossi:

Well, we originally had approvals in patients whose myeloma three or four times. But, in 2024, now the two commercially available CAR T products, one ide-cel (Abecma) and the other cilta-cel (Carvykti), are now both approved in earlier lines. So, we actually could potentially be eligible for CAR T after your first relapse. As long as you’ve had a number of therapies up front.  

Jamie Forward:

Okay. And so, when you say lines of treatment, that’s basically the number of therapies you’ve had so far? 

Dr. Adriana Rossi:

Right. The number of times the myeloma has come back. So, regardless of whether it’s one drug or three drugs together – we now often use four drugs together.  

But, we start off with a certain amount of myeloma and we treat it until it’s in remission as deep as we can. And then, we try to make that remission last as long as possible. Unfortunately, myeloma tends to eventually make its way back. That’s called the relapse. And then, you would start a new line of therapy. So, once the myeloma has come back after treatment, CAR T would be an option.  

Jamie Forward:

Okay. So, obviously a care partner is a part of this process, as is today’s focus of the program. So, can you walk us through the role of a care partner of a patient who’s receiving CAR T-cell therapy? 

Dr. Adriana Rossi:

Absolutely. And, many patients and their families will have experience with stem cells. I think the first thing to keep in mind is this is nothing like a stem cell transplant. Yes, there are cells that are collected. There’s chemotherapy and the cells are infused in a hospital setting. 

But, other than that, they are really very different experiences. And, given that’s what we would consider a long journey of CAR T through apheresis, which is the collection, then a bridging therapy while the cells are in manufacturing. Then, the hospital stay, and then the monitoring after. I think all of that is not a solo undertaking, and it really is essential to have one or more caregivers in that setting.

It’s really important to have a second set of ears at the consultation so that that amount of new information, all the big words, how things go together, meeting people is a little less overwhelming. The whole getting ready for the CAR T. There are a lot of different doctors’ appointments. We like to check that hearts and lungs are healthy. A dentist needs to check you out and make sure there’s no infection. So, just an overwhelming process. 

And, every step of the way, that’s going to be made easier if you have someone by your side.  

Jamie Forward:

Sure. It sounds like there’s a lot of coordination that takes place, as well. So, an extra set of hands is always useful there.  

Dr. Adriana Rossi:

Yeah. 

Jamie Forward:

Great. So, the care partner is a key member of the healthcare team as we established. So, who are the other members of the CAR T-cell therapy healthcare team?  

Dr. Adriana Rossi:

Yeah. It’s really important to recognize just how big that team is. We always have the CAR T physician. That one’s easy. A physician is usually supported by nurse practitioners or physician assistants and nurses that are part of again, getting all of the appointments organized. In all of this, we tend to have CAR T coordinators. Both to make sure the paperwork and the insurance side of things are done. The clinical appointments. But, it’s also important to recognize, as we were talking about, coordination. Transportation. Sometimes, patients need to stay close to a center that’s far from home. 

So, social work and all of those folks become very important. And then, there are a number of different steps with different drugs. So, our pharmacists are very important. And then, beyond that, any of the other doctors that keep our patients optimized. So, if there’s a cardiologist, a pulmonologist, an endocrinologist. All of those physicians working together. 

Jamie Forward:

Sure. As you’re preparing for the CAR T process and you’re meeting with patients and their care partners, what sort of advice do you give them about the process as you’re setting the stage?  

Dr. Adriana Rossi:

Yeah. I think it’s very important to ask questions and never think there’s a bad question, or a stupid question, or whatever. There are no limits. I know this is a completely new language, and I think it’s important even if you’ve asked it before, keep asking until it’s clear.  

And, don’t ever think you’re bothering us or anything. I’ve heard that, and it just doesn’t compute on our end. We are here to teach and support. Secondly, to take time. I think it’s really important to not think, “Oh, I’ll do this, and then I’ll run off and do something else, and then I’ll come back.” Or, have other commitments. Really allow both the patient and the caregiver protected time to be together and to just go through everything that this journey requires. And, for the caregivers to look after themselves. I think it’s really important when you’re trying to take care of someone who has the label of patient, you need to take care of yourself, as well so that you can then be of use to the process.  

Jamie Forward:

That’s great advice. So, as I mentioned, now we’re going to sort of walk through the steps of the CAR T process and what happens in each step, and how the care partner can support the patient during this time. So first, is there a consultation once a patient has been approved for this therapy?  

Dr. Adriana Rossi:

Absolutely. There are several consultations. The first one, once the patient’s identified by a referring physician, they will come and meet with myself and again, the coordinators and several members of that team to make sure that it seems like a good fit. That this is the right time, and identify any steps that we can take to really set that patient up for success.  

Jamie Forward:

Okay. And, how can the care partner participate in this meeting? Are there key questions they should be asking? 

Dr. Adriana Rossi:

Absolutely. Again, this is the beginning of the journey, and they should absolutely be there. Mostly because a lot of the information, this may be the first time they’re hearing again, the words. The concepts. The timeline. So, do ask about when things are going to be happening. As the CAR T physician, I do this all day. So, it’s very clear in my mind, but until it’s clear for them, again, ask more questions. Ask for clarification. 

Be clear on what resources are available. If there’s something that there is a question like transportation, or sequential appointments, or children in the family. All kinds of things. Really be as curious and as vocal as you’re up for. 

Jamie Forward:

Right. Arranging for childcare and pet care is probably really important during this time. 

Dr. Adriana Rossi:

Exactly. 

Jamie Forward:

What about financial planning? Is that a good time to ask about insurance and who to coordinate with there? 

Dr. Adriana Rossi:

Absolutely. Again, you will meet with social work. But, if there are specific issues that we’ve already identified, specific resources, specific paperwork, we can get that started right away.  

Jamie Forward:

Okay. Great. So then, after that, once all of that has been squared away and you’re ready to go into the CAR T-cell therapy process, there’s the T-cell collection, correct? 

Dr. Adriana Rossi:

So again, to distinguish it from stem cells, I think it’s important to know it is a one-day collection for CAR T. 

There are no injections or other preparations ahead of time. There’s no minimum number of cells that we’re aiming to get. It really is a one-day commitment to collect the cells that we collect, because they’ll be then engineered and modified before they’re ready. And so, it’s not the ordeal that sometimes you have to go through for stem cells.  

Jamie Forward:

Okay. So, the care partner should just be there during that time to be a supportive loved one. 

Dr. Adriana Rossi:

Exactly. And, it can be a long day. You’re tethered to the machine for a few hours. And, when all goes well, it is an exceedingly boring experience. So, be entertaining and be nearby. Always helpful.   

Jamie Forward:

That’s great advice. So, once the cells have been collected, can you walk through the next steps? I believe there are bridging treatments involved. Are those administered inpatient or outpatient? 

Dr. Adriana Rossi:

Absolutely. Bridging therapy is the therapy the patient receives while the cells are out being manufactured. And really, the goal there is not to get rid of myeloma. It’s just to prevent it from growing. Because myeloma that is not cared for tends to grow quite quickly. There are options to do it inpatient. To do it outpatient. There are certain therapies that would require the patients come to our center. Others that are easily given with their local oncologist. So, we really try to find something that the myeloma will be sensitive to, and that will hopefully not be too toxic, so there’s not a big recovery or a big downtime as we are preparing for the hospital stay for CAR T. 

Jamie Forward:

Okay. And, how can care partners support the patient at home during this time? I would imagine it’s sort of an anxious time. 

Dr. Adriana Rossi:

Absolutely. Many times, the bridging is something that may be familiar. Like, we’re recycling drugs they’ve seen before.  

But, these could be brand new drugs. And, I think every time you’re experiencing a new cocktail, there is some learning of how will you react, and the anxiety that can come with that, as well. There are a few times when there are delays in the cells getting ready. So, it’s not a very exact day, and that waiting period, wondering will they really come on the day they’re expected absolutely could be an anxious time. I think keeping each other company and just actively working to be your healthiest self for whenever the CAR T is ready, and knowing that working with your physicians, we are all working behind the scenes to work to the greater success hopefully is helpful.  

Jamie Forward:

Okay. That’s great. And then, finally in the process, the cells are infused back into the patient. Since this is a critical time for patients, how can care partners best be prepared to help their loved one 

Dr. Adriana Rossi:

One of the most common side effects is something called CRS. 

Which patients experience as a fever. And, I think many times in blood cancers, we really worry about fevers, because those could be infections. I think it’s important to be prepared and expect the fever so that again, it’s not oh no, what is this? We were waiting for it. It tends to come at a very scheduled time dependent on the product. So, just reassuring. Remembering yes, there are toxicities, but they are expected. Plan for them.

The medical team will have an antidote. We’ll have steps that we take depending on what comes up. And, the reason for being in the hospital is exactly to allow the medical team to respond very quickly. Most of the time, very little happens, and that is wonderful. So, if anyone is feeling bored, that is great. Celebrate it with them. No news is good news during the couple weeks in the hospital.  

Jamie Forward:

Okay. And, how long is the patient monitored for side effects in the hospital following new infusion? 

Dr. Adriana Rossi:

So, depends on the product. Ide-cel tends to have very early reactions. And so, our policy is one week for ide-cel and two weeks for cilta-cel because there, most of the side effects are around seven days in. So, we wait for the inflammation to peak and resolve. And, once it’s safe, we aim to get patients home. But, once they leave the hospital, they should for at least a few weeks be very close to the CAR T center, and usually require two to three visits a week for that close monitoring. 

Jamie Forward:

What are the short-term side effects associated with CAR T-cell therapy?  

Dr. Adriana Rossi:

Absolutely. So, the T cells are part of the immune system. Their job is to grow and expand once they’re in the patient, and pick a fight with the myeloma, which will cause a certain level of inflammation. So, some inflammation is good. But sometimes, they overdo it, and it manifests itself as a fever. We call that cytokine release syndrome. Cytokines are the molecules T cells use to communicate with other members of the immune system. So, this is part of the process we are causing, but we want to keep it in check.  

And, in the early days, we were very hesitant to do anything that could harm these precious T cells. But, we’ve learned in time that all of the antidotes, including tocilizumab-bavi (Tofidence) and steroids, don’t harm the effectiveness of the CAR T. And so, we’re very quick to intervene early and intervene with as many tools as we need. And so, that’s really become mostly just the fever. If left untreated, it can lead to low blood pressure and maybe an oxygen requirement. 

Again, usually quite easily reversible. When the inflammation happens around the brain or the nerves, we call that neurotoxicity. Specifically ICANS, which is the confusion and neurological deficits that occur with CRS. Neurotoxicity also includes other things like a peripheral neuropathy, cranial nerve palsies like Bell’s palsy has been reported quite frequently. And then, very rarely, delayed neuromuscular toxicities, which again, by patient selection are becoming more and more rare.  

And, the last is low blood counts, which we’ve touched on as part of the reason patients need such close follow-up once they leave the hospital. They’re very much at risk for infections, because they’re not making antibodies. Their neutrophils, which is the infantry type white blood cells, are low. And, their T cells are going to be low from the process. 

Jamie Forward:

Okay. And so, for a care partner, what should they be looking for? And, when should they contact a member of the healthcare team? 

Dr. Adriana Rossi:

I would say contact us anytime there is a question. It’s not too specific. Certainly, any fever. Any sign or concern for infection. And, any neurologic deficit. If someone is not acting themselves, the caregiver’s usually in the best position to recognize that. 

Jamie Forward:

Okay. And, what are the long-term side effects?  

Dr. Adriana Rossi:

Yeah. We’re still learning. Beyond a year, really there shouldn’t be many. We continue to support the patient until recovery of those antibodies, and T cells, and neutrophils. So, there’s a lot of preventive things. Monitoring and time. And, there are these rare neurological toxicities that have been reported, but they’re much less than one in 1,000. And so, it’s hard to learn or to make any generalizations at this time. 

Jamie Forward:

Okay. And, as far as monitoring at home once someone gets back home, in the weeks that follow their time in the hospital, are there certain supplies they should have? It sounds like maybe blood pressure? Perhaps a scale? 

Dr. Adriana Rossi:

Yeah. So, blood pressure and temperature probably are the two more important ones. We actually do discharge patients with a log, and for those first few weeks, we really would like at least twice a day for these numbers to be monitored. And, it’s patient-specific. So, the less you need, the more we graduate out to fewer measurements and less monitoring.  

Jamie Forward:

When it comes to diet and nutrition, are there ways that care partners can help prepare or benefit to a highly nutritious diet? Is there anything related to diet and lifestyle that might be important to know? 

Dr. Adriana Rossi:

No. I think there’s no restriction. The important thing is when your appetite is low, your body needs calories. We’re asking your body to get a lot of work done, and it can’t do that without calories. So, don’t be too picky on only eating fruits and vegetables. If it’s ice cream three times a day, go for it. Make sure you’re meeting a caloric intake. Certainly, nutrition is better. The only dietary restrictions we have are really kind of similar to after a transplant where we’re trying to avoid germs. So, foods that can be cooked, peeled, or washed are really the focus. Things like berries and salads can easily have germs sneak in. So, we do try to avoid those. And again, it’s usually just for that first month or two. Recovery tends to be quick. 

Jamie Forward:

Okay. Great. So, have a lot of ice cream on hand. So, how do you know if the treatment’s working? 

Dr. Adriana Rossi:

Well, most patients will have an M spike or light chain change. So, we can follow that by blood tests. And, as with any other therapy, it’s usually a monthly check of those numbers. 

And then, we follow the paradigm we see in stem cell transplants at around day 100 doing a bone marrow biopsy and a PET scan. 

Again, up to 90 plus percent of patients, will have a complete remission on their blood tests within a month. But, we wait until day 100 to really let that protein have time. There’s a certain time to clear from the system. Check the cells in the bone marrow and really give you full credit for all your efforts.  

Jamie Forward:

Okay. Great. So, we’ve sort of touched on this before, but I think it bears reiterating. So, why is it so important that care partners let the care team know about any changes they see in their loved one? 

Dr. Adriana Rossi:

I think early intervention really leads to success. Most of the toxicities will respond very well to an early intervention. If left untreated, be it an infection, a neurologic finding, a cell count issue, the longer it happens, the bigger of a problem it is, and the harder it would be to turn around. 

So, something that could hopefully be a quick visit to the office could then become an admission to the hospital, and we’d really like to prevent that.  

Jamie Forward:

Okay. Great. So, let’s talk a bit about self-care for care partners. I think this can obviously be a really taxing time. Why is self-compassion essential during this time when you’re caring for someone else? 

Dr. Adriana Rossi:

Because many times, again, the focus is on the patient. But really, we need to recognize it’s stressful for all of us. And, the whole medical team is taking care of the patient. Very few people are paying attention to the caregiver. So, they really need to be able to ask for help. Hopefully, again, it’s not a one-man job. It’s rally the village around the person. We do ask for those first few weeks that it’s 24 hours a day the patient be with someone. But, it doesn’t have to be one person. So, have someone else come in, so you can go exercise, or go get a cup of coffee, or just spend time dedicated to self-care. So that then you can be as strong and as present as you can for the patient. 

Jamie Forward:

And, what are signs of burnout? How can care partners recognize that? 

Dr. Adriana Rossi:

Very hard to recognize, and usually it’s someone else who needs to point it out. But, emotional exhaustion I think is the most common, because it is such an emotionally taxing time. So, having a difficult time concentrating. Being irritable or pessimistic when sometimes the medical’s team’s like, “Everything’s going great.” And still, you’re like, “No. But, it’s not going to last.” Putting a negative twist is usually part of that. You just don’t have the reserves to look forward. And then, changes in sleeping, or eating, or regular habits can also be a flag. 

Jamie Forward:

And, what advice do you have for care partners to make time for self-care? When can they find those spaces for themselves? 

Dr. Adriana Rossi:

I think the biggest thing is to not think that it’s being selfish or that you’re taking away from the partner. 

Think of it as something you are doing for the patient. You are not useful if you’re burnt out and if you’re spent. So, self-care really is a giving activity of strengthening yourself so that you can then be of most use to the patient.  

Jamie Forward:

I think that makes good sense. So, there are obviously social workers at the centers, and obviously these larger CAR T-cell therapy centers have a number of resources. So, what is available to help care partners during this time?  

Dr. Adriana Rossi:

So, social work will meet with the patient and the caregiver to tailor resources, and plans, and support in any way that is specifically useful to them. 

Again, if there is specific paperwork that needs attention. If there are resources, for example, lodging, transportation. All of these things are really tailored to the needs of each individual.  

Jamie Forward:

Okay. And obviously, this isn’t for everybody, but support groups are always a good idea, even if online. 

Dr. Adriana Rossi:

Absolutely. And, we have a number of those. We’re lucky to have a group of social workers, and they each lead different groups. So, if one doesn’t seem to be a good fit, I also think keep looking. There are very specific ones like younger patients or patients of any particular group. But, there are also general patients. There are transplant-specific. And, more and more, there are CAR T-specific groups where patients share their experience. 

Jamie Forward:

Yeah. It’s always nice to know that you’re not alone in these situations.  

Jamie Forward:

So, are there in-home services that can be useful for CAR T-cell therapy care partners during this time?  

Dr. Adriana Rossi:

I’d have to say that’s probably very specific to geographic areas. I happen to work in New York where there are a lot of home services, and it’s very population-dense, and a lot of the services are driven to that. I imagine in parts of the country where there’s quite a bit of distance between the facilities, there are probably programs that are more structured to provide those services. So, that’s probably fairly program-specific. But generally, yes. I just don’t know what they are for each part of the country. 

Jamie Forward:

Before we move on to audience questions, I’d like to add that the Patient Empowerment Network has a wealth of resources available for care partners. You can find those at powerfulpatients.org or by scanning the QR code on your screen.  

Dr. Rossi, here’s a few questions we received in advance of the program from our members. We can start with William’s question. How can a care partner manage the emotional aspects when a loved one is going through CAR T? 

Dr. Adriana Rossi:

I think be patient. Recognize that it’s a really difficult time, even when everything goes according to plan and the medical is very pleased that there’s nothing untoward. It’s just a really stressful time for both of you. So, it’s where we go back to the self-compassion, as well. Take time for yourself and recognize your needs as a caregiver in addition. So, tapping in, again, other friends. A small circle rather than a one-person job. And, being really open with social work on what resources can be helpful. Asking for help, again, is a brave act.  It’s not a sign of weakness at all. 

Jamie Forward:

Sure. And, I think it’s often that people will offer help, and you tend to decline because you think you can handle it early on. And, it is just so much easier to say yes. Say, “Yes. Bring over dinner.” Or, “Yes. I’d love you to come over for two hours while I go out and have a pedicure.” So, yeah. Always say yes when people ask you if they can help, because people want to help. 

Dr. Adriana Rossi:

Exactly. And then, it is that group activity, and it’s a shared experience. 

Jamie Forward:

Yeah. Okay. So, Marianne asks this question. She says how do the aftereffects of CAR T-cell therapy compare to those of stem cell transplant? 

Dr. Adriana Rossi:

Yes. Very different experiences. I think that’s one of my first and loudest messages. Stem cell transplants are really tough. Melphalan (Alkeran) is a very tough drug. The hair loss, the nausea, the weight loss we really do not see with CAR T.  

So, we mentioned you have to have your cells collected. You do get some chemo before getting the cells back. But, that’s as far as they are similar. The chemotherapy that you get before CAR T is called lymphodepletion. It only quiets down the T cells. It’s not a rebooting of all of the marrow the way we do with melphalan. And, the side effects are again, mostly driven by inflammation. So, fevers and neurologic deficits. Remembering that the fevers and CRS are expected in about 80 percent of patients. The neurologic side effects are in under 5 percent. So, much more rare. And, it’s usually with transplant, by day 100, if people were working before their transplant, they start to think of going back. With CAR T, I have patients who are 30 days out asking to go back to work, because they’re bored at home. You really just feel better much sooner.  

Jamie Forward:

Okay. That sounds like a pretty dramatic difference. And, here’s the last question we have from Debbie. She wants to know does the caregiver need to stay at the hospital room with the patient,  or are they only allowed during visiting hours?

Dr. Adriana Rossi:

I think that one is very specific to the center. At Mt. Sinai, we do have specific visiting hours. And, a few exceptions have been made for overnight depending on the specific circumstance. But, most of the time, that is a time the caregiver can go home, and sleep, and be ready at the time of discharge when we really do need them 24 hours.  

Jamie Forward:

Okay. That’s good to know. So, it’s center-specific. Great. So, before we end the program, I’d like to get your closing thoughts on the role of the care partner in the CAR T-cell therapy process. What message do you want to leave our care partner audience with? 

Dr. Adriana Rossi:

I think mostly to please reach out to us. 

We are there not only to take care of the patient, but the global patient experience. So, we are there to support the caregivers, as well. So, please ask questions. Many times, I’ll have had a conversation with a patient many times, and then the caregiver joins later and is hearing everything for the first time. So, please ask questions until everything is clear. And, remember to look after yourself. 

Jamie Forward:

That’s great advice. Thank you so much, Dr. Rossi. We appreciate you being here today. 

Dr. Adriana Rossi:

Thank you.  

Jamie Forward:

And, thank you to all of our collaborators. To access tools to help you become a proactive care partner, visit powerfulpatients.org. Thanks for joining us.  

Evolve | What You Should Know About Advances in CAR T-Cell Therapy for Myeloma

How is CAR T-cell therapy revolutionizing care for people with myeloma? Dr. Rahul Banerjee, a myeloma expert and researcher, shares an overview of how CAR T-cell therapy is evolving, important factors to consider when choosing to undergo this treatment, and how advances in research are impacting myeloma care. 

Dr. Rahul Banerjee is a physician and researcher specializing in multiple myeloma and an assistant professor in the Clinical Research Division at the University of Washington Fred Hutchinson Cancer Center in Seattle, WA. Learn more about Dr. Banerjee.

Download Resource Guide

Related Resources:

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care? 

Transcript:

Katherine Banwell:

Hello and welcome. I’m your host, Katherine Banwell. Today’s program is part of the Patient Empowerment Network’s Evolve series, which was developed to provide you with the latest treatment information and research, helping you to feel empowered and confident during conversations about your care. In today’s program, we’re going to hear from an expert in the field discussing CAR T-cell therapy and the evolving treatment landscape. 

Before before we get into the discussion, please remember that this program is not a substitute for medical advice. Please refer to your healthcare team about what might be best for you. Joining us today is Dr. Rahul Banerjee. Dr. Banerjee, it’s so good to see you. Welcome. Would you please introduce yourself? 

Dr. Rahul Banerjee:

Of course. Thank you, Katherine, for taking the time to interview me. Thank you to everyone who’s listening. My name is Dr. Rahul Banerjee. I’m an Assistant Professor of Medicine at the Fred Hutchinson Cancer Center in Seattle, Washington.  

I specialize in multiple myeloma, which is a form of blood cancer that we’ll talk about, and other precursor conditions, for example, smoldering myeloma and AL amyloidosis. I have a heavy interest in CAR T therapy and bispecific antibodies and other types of immunotherapy for blood cancers, and I’m sure we’ll be speaking about that as well. It’s great to be here. 

Katherine Banwell:

And thank you so much for taking time out of your busy day. I’d like to start by talking about your role as a researcher. You’re on the front lines for advancements in the myeloma field. What led you here, and why is it important to you? 

Dr. Rahul Banerjee:

Absolutely. So, the short answer is that I love the art and the science of oncology, of cancer care. I feel like it really gives us a great chance to work with patients and really help them through the difficult chapter of their life. And the science, particularly in malignant hematology, is a word we use for blood cancers like myeloma, lymphoma, et cetera. There’s a lot of fascinating science about how do we train the immune system to overcome cancers of immune cells? 

In terms of why myeloma, you’ll probably hear this from many physicians who speak on this program. Part of it is the patients, and I love treating my patients with myeloma. They have the most interesting stories for me. Many of them are older and have been through a lot, and I worked with them for years for diagnosing myeloma, treating them through myeloma, monitoring for relapses, and so forth. 

And also the mentors whom I had. So, when I was a trainee in fellowship, I was not sure where I would go. I knew it was somewhere within blood cancers, but I had a mentor, Dr. Nina Shah, who is phenomenal, and she did a lot of work in multiple myeloma in particular, including around CAR T therapy, and I kind of molded myself, imprinted myself on her. And now several years later, here I am kind of working in this similar space, focusing again at the intersection of multiple myeloma and these immunotherapies, like CAR T therapy. 

Katherine Banwell:

We’ve been talking about CAR T-cell therapy for a number of years now. How has this treatment revolutionized care for patients? 

Dr. Rahul Banerjee:

Absolutely. So, the biggest benefit of CAR T therapy, I think, is how well it works. So, I’ll predominantly focus on multiple myeloma, but of course there are CAR T therapies that are approved for different kinds of lymphoma, and B-cell leukemia as well. But in brief, CAR T therapy, we train the immune system to fight back against the myeloma, against the cancer that’s there. And it’s phenomenal, because it’s the only living drug we have, really, in our toolbox. Everything else is dependent on the dose, right? As soon as the drug is out of your system, it stops working. CAR T-cells don’t work that way. They can live and expand and proliferate to get rid of the threat within. 

And at least in myeloma, for example, CAR T therapies regularly have response rates, meaning complete response rates, how quickly they knock all the myeloma parameters down to zero basically in the 70, 80, 90 percent range. Many patients achieve measurable residual disease, or MRD negativity, meaning by all the best tools available in 2024, no sign of the myeloma anywhere.  

That doesn’t mean cure, to be fair, but that’s wonderful. With other conventional therapies, to have one drug with one infusion have that big of an impact on the myeloma is phenomenal.  

The other benefit of CAR T therapy is that it is a one-time infusion. It doesn’t mean that patients can get one-time CAR T and never have to see a cancer doctor again because again, at least in myeloma, I don’t consider CAR T to be uniformly curative for patients. However, if you look at the studies, and there’ve been two randomized studies in myeloma of CAR T therapy versus standard therapies. One was a KarMMa-3 trial with a drug called ide-cel, a CAR T drug also known as Abecma. And the other one was CARTITUDE-4, which was a study of cilta-cel versus standard treatment. And cilta-cel is a kind of CAR T also known as Carvykti.  

Both studies saw improvements, dramatic improvements in the response rate, how many patients had the myeloma numbers come down, but also durations of response and progression-free survival. How long patients were alive and disease-free for.  

Literally just a month ago, we found out officially that the cilta-cel trial and the CARTITUDE-4 study, CAR T actually prolonged overall survival compared to standard therapies, which is what patients are looking for.  

But for me, what I love about CAR T the most is not just that you’re in remission for longer, or with cilta-cel you live longer, but that you live better. Both studies, and I’m very happy to see this incorporated, what we call patient-reported outcomes, which is an area of research of mine. Patient-reported outcomes are, as you can imagine, outcomes that are reported by the patient. Not the blood test for the myeloma, but how are patients feeling in terms of their quality of life, in terms of their fatigue, in terms of their pain.  

And in both studies, off the charts. CAR T does way better and way faster in terms of improving quality of life than standard treatments, to the point where the studies, for example, often for both of them, if I recall correctly, the first time point where they looked and compared the two arms was three months after CAR T. And already by then, night and day difference.  

The patients who got CAR T, the first month a little bit rocky, but after the first month or two, they’re doing better, because they’re not on myeloma treatments continuously. They’re still getting blood work checked and so forth, but they’re not on treatment. It’s a one-time infusion and monitoring thereafter. 

And I love that about it, and I think that explains a lot of the quality of life benefits that we see.  

For my other patients with myeloma, outside of CAR T, there is never a scenario where they’re observed. The vast majority of patients because myeloma is considered incurable, we keep them on some form of maintenance treatment, and those come with side effects. Those come with financial toxicity. That’s the word we use for high out-of-pocket costs. They come with what I would call time toxicity. That’s time spent on the phone coordinating shipments or coming in for this infusion or that infusion. 

CAR T has much less of that, and I think that’s phenomenal. So, I would say that it’s revolutionized the field, not just scientifically from the things that you’d expect a researcher to care the most about – for how long, you know, how deep are their remissions and how durable are their remissions, but also for the things that I care about. The art of oncology is how our patients are living, and that’s why I think CAR T is revolutionary. 

Katherine Banwell:

Dr. Banerjee, would you walk us through the currently approved CAR T-cell therapies for myeloma and share how these treatments work to combat myeloma? 

Dr. Rahul Banerjee:

Absolutely so. So, there’s two FDA-approved CAR T therapies right now for multiple myeloma. One is ide-cel, also known as Abecma. One is cilta-cel, also known as Carvykti. The mechanics of them are pretty similar. Both involve T-cells being collected from the patient and then turned into CAR T-cells, cancer fighting cells in a lab, then put back into the patient after a small dose, what we call lympho-depleting chemotherapy, that creates a void and makes room for the T cells. 

And then the T cells come in and are able to activate and proliferate and respond and kill off the myeloma. In terms of the two drugs, the differences between them, we might come back to that a bit in terms of just how they’re approved. Cilta-cel is currently approved as early as first relapse. So, second line treatment onwards in myeloma for patients who have disease that is refractory to lenalidomide (Revlimid) or a similar class of drugs.  

So, lenalidomide is Revlimid. So, if someone’s been on Revlimid and it stopped working, they could technically go to cilta-cel, which is Carvykti, as soon as second line. 

Ide-cel or Abecma is approved for third line treatment, meaning at least two prior relapses or two types of therapy that were stopped unexpectedly because of not working or toxicities or so forth. And those patients would have had to have received both an iMiD, like Revlimid, which is lenalidomide, a proteasome inhibitor, which is like Velcade or bortezomib, and a CD38 directed monoclonal antibody like daratumumab, which is also called Darzalex or Darzalex Faspro.   

Katherine Banwell:

CAR T therapies have been in use for several years now. As a clinician, what challenges are you facing with this treatment option? 

Dr. Rahul Banerjee:

Absolutely. So, I would say threefold, is the best way to describe it. So, I think the first and most practical, like the most important one is obviously access. It’s very easy for me to talk about CAR T therapy. I had the privilege of working at a big center, where I was just last week attending on our CAR T service. We’re big enough to have a CAR T service. 

Most patients are treated in the community, and they don’t have access to a doctor who’s personally familiar with CAR T. And so for them to get to CAR T requires a move to a big academic center, a big tertiary care center. Obviously, I think this talk is geared more towards the U.S. audience, but most of the world has no access to CAR T, period, except for research protocols, and that makes things really tough. So, I think that’s one unmet need in general, where those patients who cannot get to CAR T never see me, and that’s a big disparity in the field.  

Two, I would say that the autologous CAR T products we have, autologous is the word that we use for the T cells that are coming from the patient themselves. Both Abecma and Carvykti, again, it’s the patient’s own cells that are being taken out, turned into CAR  
T cells, and put back. That manufacturing process takes time. Typically, I tell patients to expect about one to two months, closer to two months often, between the day that the T cells are taken out and the day they’re put back in again, what we often call the quote unquote “vein-to-vein interval.” And that’s hard because for some patients that’s not practical. 

The myeloma is, you know, so aggressive, behaving aggressively, that they cannot wait. There’s no drug I can give them where I can wait two months for the T cells to be manufactured. We’re getting better at it. The drug company is working better at it. There are a lot of investigational products that are not FDA approved yet that are looking at rapid manufacturing, where can you grow these  
T cells and the CAR T cells in two days or one day, instead of several weeks? I think that’s really interesting. 

There are studies of allogeneic CAR T cells, where the T cells are pre-manufactured from a healthy donor and manipulated so they won’t cause any other problems, but will attack the myeloma. So, a lot of research happening there, but that’s the problem for patients where they cannot get to CAR T therapy.  

And then the third unmet need would be – I’m seeing more of this, unfortunately, right? CAR T therapy is not considered curative for myeloma. Have I met people who are doing great years out from myeloma? Yes, from CAR T therapy, and I love that. In the original LEGEND-2 study, the study that led to the CARTITUDE-1 study that led to the approval of cilta-cel, which is Carvykti. 

If I recall correctly, about 20 percent of patients on that first Chinese study years ago are alive and disease-free five years later. That’s not enough, right? I don’t want it to be 20 percent, I want it to be 100 percent. And so we have work to be done there in terms of what do we do when the myeloma, the CAR T cells stop working, or they’re out of the system and are no longer there to fight back. What do we do next? And I think that’s another unmet need still. Despite all the advances, what to do after CAR T, no one really knows. 

Katherine Banwell:

Yes. Well, how is success measured for CAR T-cell therapy? 

Dr. Rahul Banerjee:

It’s a great question. So, traditionally, the metric in multiple myeloma has been achieving a complete response. So, having the M-spike, the antibodies that are produced by the myeloma cells, come down to zero.  

So, either the M-spike, or for some patients, that may be the kappa or the lambda, which are fragments called light chains of antibodies, coming down to the normal range. The hard thing about those is that they take time. I’ve had patients who get CAR T therapy, and their bone marrow is completely clear, including MRD, measurable residual disease, as I’ll talk about in a second, but the M-spike takes months. 

I had one patient where it took a year and a half for the M-spike to finally come down to zero. And it’s frustrating because I would say that, look, in my heart, you’re in remission, but if I were a lawyer, I wouldn’t be able to say that, because technically the M-spike is not quite zero yet. Your body’s just recycling that antibody. It’s not all the way down to zero, and that makes things tough. So, I don’t think that’s a great barometer to use.  

I think MRD, which is again, a bone marrow test that we can spend more time talking about another day, is helpful. And at the one-month mark, achieving MRD negativity.  

So, if you look in the bone marrow, by all the best tests available in the United States in the year 2024, and you can’t even find one out of a million cells that are myeloma, that’s obviously great to see.  

That doesn’t mean that if it doesn’t happen, the patients are going to do poorly. There’s a lot more to CAR T than that. So, I think MRD negativity is probably the best short-term barometer. I think the best long-term barometer would be progression-free survival, which is, again, the medical word of saying how long is someone alive and in remission for. 

With cilta-cel, which is Carvykti, again, in the CARTITUDE-1 study, which led to its approval, its first approval for four prior lines of therapy. There, most patients, the median progression-free survival was 35 months. So, almost three years. That’s amazing, right? Three years of mileage of coming in for blood work, some supportive care, IVIG, which is a type of antibody transfusion, but not needing myeloma treatment. That’s great. That’s the bar that we’d be looking for from an efficacy perspective. I think the other thing, just to talk about it, I’m sure we’ll come back to it, would be safety, right? Because these cells, these therapies do come with side effects.  

And so I think the other bar by which, in the future, I may compare CAR T therapies as more come to market, would not just be this progression-free survival, which is how long are patients in remission for and disease-free and alive. Not just MRD negativity, which is how the bone marrow biopsy looks at day 28, one month after CAR T. But also the safety profile. Are we seeing any scary, concerning, delayed toxicities? And if we don’t, that would be another bar for success in my mind, especially as we move CAR T to earlier lines, where other treatments are available. 

We have to make sure that the benefit-risk ratio for CAR T remains favorable. 

Katherine Banwell:

Yes. Well, let’s talk about side effects of CAR T-cell therapy. What advances are being made in managing them? 

Dr. Rahul Banerjee:

Excellent question. So, I break the toxicities into short-term and long-term toxicity of CAR T therapy. And this is actually fairly similar for both, regardless of the underlying disease, whereas lymphoma, leukemia, or myeloma, very similar. Just so everyone, just to reorient the audience, short-term toxicities, people often talk about the big two. I’m going to say the big three, actually. The first one is cytokine release syndrome, or CRS, which is inflammation, typically causing fever, sometimes low blood pressure. 

The second is neurotoxicity, or ICANS. For reasons that aren’t entirely understood, sometimes all those chemicals from inflammation can cause people to feel a bit off mentally or cognitively. Sometimes people might not be able to talk, or might not talk correctly, or sometimes have issues along those lines. 

And the third, I would say, is low blood counts or infections. Both the lymphoma, leukemia CAR Ts and the myeloma CAR Ts very rapidly deplete the good plasma cells or the good lymphocytes, the good cells in the bone marrow, and so immediately you see patients at risk of infections. 

And for a complicated number of reasons, one of which being cytokine release syndrome, CRS inflammation within the bone marrow, where all these cancer cells are hiding, the stem cells in the bone marrow hide away, right? They kind of go into a bunker to stay away from all of this. And so patients often have low blood counts for significant amounts of time after CAR T therapy, something called hematotoxicity. 

Those are short-term toxicities. Long-term, very briefly, that risk of infection and low blood counts is still there, I would say, for up to a year after CAR T therapy, sometimes longer for some patients. There is a risk, obviously, of the original cancer coming back, in this case the myeloma, particularly myeloma.  

And three, there are rare delayed toxicities to be on the lookout for. So, one of them, for example, with cilta-cel or Carvykti, the numbers are hard to see what the rate is prospectively because it’s been going down with time.  

But rarely, I would truly in my heart say 1 percent of the time, if not less, patients can get Parkinsonism, where they’re not able to move as rapidly, they’re not able to, they’re kind of shuffling gait, having tremors, et cetera. Not the same as normal Parkinson’s disease, because the normal meds don’t work, just time is often the only thing that really makes a big difference. 

Technically, there’s a box warning on all CAR T therapies now about a risk of second cancers. That risk is not new to anyone who’s ever received any treatment for myeloma because from the very beginning, we tell people that these drugs have been linked to a potential risk of second cancers in the future.  

In terms of strides that are being made to improve that, I think we’re making a lot of improvement. So, I think the biggest thing that we’ve learned, and I remember when I was a trainee, for example, when I was in my medical training, the early days of CAR T therapy – actually out in Philadelphia, I trained at Penn – and there, we were scared about trying to tone down the inflammation.  

When these side effects happen in the short term, the goal is if the patient’s obviously having side effects, and the question is, “Can we not kill the T cells? Can we just dial that down?” Say, “Look, I’m happy the T cells are angry. I’m happy they’re killing the cancer, the myeloma in this case. But can you just dial it down a little bit with a medication called tocilizumab (Actemra), or corticosteroids like dex?” 

We used to be very nervous about doing that because we said, look, the patient’s put all this blood, soil, sweat, and tears right into this CAR T therapy, and we don’t want to do anything that can hinder the T cells from working.  

Now we know that that level of inflammation is not doing anyone any favors at all, and so we’re able to really start these medications to just dial down the immune system faster. As soon as someone has a fever, for example, at many centers, we do consider, within an hour or two, giving one of those medications. Don’t wait till they’re in the ICU, give it then.  So, I think just tweaking our algorithms has made probably the biggest difference, in my mind, to make CAR T safer.  

Other things that have helped, I think, are better understanding of why patients have these other toxicities and strategies to prevent it. And so, for example, the neurotoxicity risk, some of it is part of disease burden. We think that patients who have a lot of disease going into CAR T therapy may have more toxicities. So, giving better treatments as, quote-unquote, “bridging treatment” before CAR T therapy that we have better, newer treatments now, have sometimes helped to really debulk the disease before going to  
CAR T.  

That’s helped a lot with side effect management. In terms of long-term risk, the third thing that I really encourage all my patients and all my oncologist partners in the community to really push for is the infection risk and how do we prevent it? So, I think probably the biggest thing that we’ve recognized is intravenous immunoglobulin, which is IVIg, which is basically an antibody transfusion.  

When people donate blood, they also donate plasma, often, and the plasma contains antibodies against whatever they themselves have fought off circulating in the area – viruses, colds, et cetera. 

You can take all those antibodies, put them all together into a sterile bag, and give it to the patient who’s gotten CAR T therapy. Because the patient’s gotten CAR T therapy, assuming it’s working, which it normally does for several months, right, to knock out all cells, good and bad immune cells, that patient is not making any antibodies at all. They’re a sitting duck for infections. And so I would say IVIg, using that routinely now is not just the exception once they’re having infections, but even in the absence of infections, just giving it.  

Insurance companies are not happy with me when I suggest that because it’s expensive, but that’s the right thing to do for patients, and I think that has helped a lot, in my experience, for all of these immunotherapies, both CAR T and bispecific antibodies, to lower the risk of infections.  

Katherine Banwell:

Can you share any updates in CAR T-cell therapy research? 

Dr. Rahul Banerjee:

Sure. So, several. I would say the first, I alluded to very briefly earlier, was how do we make that vein-to-vein time shorter? So, the vein-to-vein is, again, from the moment that the T cells are collected to when they’re put back into the patient.  

And so a lot of research is how do we make that better? We have rapid manufacturing protocols that, again, where the T cells are taken out and manufactured within a couple of days and brought back into the patient. They’re still testing for safety and sterility and everything that needs to be done, so it’s not overnight, but still, one or two weeks’ worth of vein-to-vein time is way better than one to two months.  

The allogeneic CAR T cells that are coming from a healthy donor, those are fascinating, right? Because if the cells are pre-manufactured, there’s no risk of them not manufacturing or manufacturing in an odd manner, what we call auto-specification. They’re ready from a healthy donor, ready to go. 

And one of the studies that was presented last month at our International Myeloma Society meeting in Brazil, the time, the median time from when the patient went on the study to when they started that lympho-depleting pre-CAR T therapy was one day, and that means they got CAR T therapy within one week of going on the study. That’s phenomenal. And so I think that research is ongoing.  

There are some side effects about allogeneic, healthy donor CAR  T-cells in terms of making sure the T cells stick around and don’t cause other issues. Sorry, for another day. I think that’s one area of research.  

I think the other big area of research is how do we make CAR T-cells work for longer for more people? There are easy ways, and there are controversial ways to do that. So, I think the easy way is can we use MRD negativity or other tests to identify who is at very low risk of relapse and monitoring them appropriately.  

There are patients where, in the future, we may talk about doing some form of post-CAR T maintenance therapy. Again, the bar for that should be set pretty high, and it is set pretty high because as I mentioned earlier, many patients prefer CAR T therapy, not just because of the deeper remissions and longer remissions, but because it truly is time away from treatment. But they’re still coming in for the IVIg and the blood work and seeing a doctor, et cetera, but they’re not getting daily treatment with lenalidomide, which is Revlimid, or pomalidomide, or Pomalyst, or something like that. And that’s wonderful. 

However, there may be some patients where some form of strategy will use one of those medications or experimental medications. There’s a newer class of the lenalidomide, Revlimid, pomalidomide, Pomalyst called CELMoDs.  

They’re not approved yet, but drugs like iberdomide or mezigdomide that work better, and not just against the myeloma. They actually make T cells stronger, believe it or not. 

And so in the future, there may be scenarios where we recommend for certain patients that, hey, in your particular case, after CAR T therapy, to keep the myeloma away, I’d recommend using this form of maintenance, a pill or something like that, just low dose to, again, keep the myeloma at bay and keep the T cells, in this case, the CAR T cells strong. So, I think those are all areas of exciting research.  

And then the last thing I would say is, we have several novel CAR T therapies that are being studied that may work better and safer than the existing products. Some of them, which are in early phase studies, actually target two proteins at once. The idea, going back to one of the earlier topics I mentioned, is that if the CAR T cells see that protein BCMA, they immediately destroy the cell that’s holding that. But what if the cell learns to turn off BCMA? All of a sudden, it’s invisible to the CAR T cells, and you’re right back to starting square one again. 

And so the idea is that there are CAR T cells that are being developed that target two proteins at once, kind of what’s called origating, where if it sees this or this, it’s immediately able to attach and bind that cell.  

The idea being that it’s easy for a myeloma cell – not easy. It’s possible for a myeloma cell, just by dumb luck, bad luck for the patient, to mutate in a way that shuts off that one protein. For it to simultaneously be able to do that for two separate proteins at once, the odds are much lower.  

And so the idea with dual targeting is you may be able to knock out more cells more durably, or even knock out the myeloma precursor cells that aren’t quite myeloma cells, but are there, what we call stem cells under the hood that are still malignant? So, a lot of those areas, I think, are really fascinating. Obviously, we need a lot more research in those particular areas before they’re ready for prime time. 

Katherine Banwell:

Yes. What is GPRC5D? 

Dr. Rahul Banerjee:

Great. Yes, so it’s a mouthful, is the best way to describe it. It’s an interesting protein. It’s a protein that, I alluded to that, it’s a second target that’s being targeted by some CAR T cells, for example, either in addition to BCMA or by itself. Several companies are looking at that in trials.  

GPRC5D is interesting because we don’t know what it’s for. BCMA, we know exactly what it’s for and why good and bad plasma cells, again, the bad plasma cells being the myeloma, why they express it. No one knows for GPRC5D.  

In the field, we’ve put almost all of our myeloma eggs into the BCMA basket, historically speaking, and all the approved immunotherapies, CAR T and bispecifics in myeloma, with one exception, which is talquetamab or TALVEY, all target BCMA. So, we need to not put all our eggs in that basket. And so GPRC5D targeted therapies, again, there was one approved bispecific antibody, which was not the focus of today’s talk, called talquetamab or TALVEY.   

There are investigational CAR T products that target GPRC5D as well. At least from the limited experience that we have, there seems to be no correlation between them.  

In the future, do we know that someone needs to get BCMA therapy first and then GPRC5D therapy later? We don’t know that, actually, and that’s one of our areas of research and one of my areas of research as well. What if we do it the other way around, right? What if we give GPRC5D first and then do BCMA? We don’t know. 

So, I think one of the big questions in the field is sequencing, which is the word of like, what drug do we use first and when? We’re working on a paper, the International Myeloma Working Group is working on a big, extensive paper to try to put all the evidence together, but that’ll be a moving target.  

Katherine Banwell:

Yes. Patient participation is essential in advancing myeloma research. How do clinical trials impact care? 

Dr. Rahul Banerjee:

Absolutely. So, phenomenally and importantly, I think it’s a short answer. It’s worth noting that clinical trials come in all shapes and sizes. People often assume that clinical trial means, by default, a Phase I study, first time in human being, a quote-unquote “guinea pig.” That’s true for a minority of studies, and that’s very important for us to understand how best to make the drug work better. I would say the vast majority of trials that I put my patients on are not like that. They’re often bigger Phase II or Phase III studies. 

As an example, you know, both Abecma and Carvykti, those were already approved in later lines, but to get them approved in earlier lines, we had to run a study of using them earlier versus not using them earlier. So, that’s a good example where the drug is FDA-approved, it’s just the sequencing of it that’s new.  

There are trials of supportive care. We’ll be opening a study, I alluded to this, the side effects of GPRC5D targeted therapies with taquetamab. We’ll be opening a study that randomizes patients to one of four different supportive care strategies to figure out which one actually works to make the taste issues better. Because we don’t know until we try, right? If we don’t do a rigorous study, and we just go by, “Oh, I had one patient once where this worked, and one patient once where this worked,” that’s not a scientific way of answering questions, and we’re not really able to advance the field to help all patients.  

So, that’s where I think clinical trials come in handy. That, and I alluded to all these newer investigational CAR T therapies that might actually work better and be safer than the existing one. They’re all coming through investigational trials.  

So, trials is kind of how we get these drugs, one, these newer ones to market, but also how we learn to make them better. And we have trials, all sorts of trials, looking at all sorts of, again, not just new drugs, but also where to put the drugs, right? Where to sequence the CAR T therapies, or what supportive care strategies do we use? And the trials are kind of the linchpin of making the field work better. Again, not just for some patients who happen to do well, but for all patients. The only reason we’ve found out what works for all patients is by doing clinical trials.  

Katherine Banwell:

I’d like to get to a few questions that we received from our audience members prior to the program.  

Dr. Rahul Banerjee:

Yes, of course. 

Katherine Banwell:

This one is from Jennifer. Why do CAR T-cell transplants not last longer? Is it possible to do a second transplant if the first CAR T transplant stops working?  

Dr. Rahul Banerjee:

It’s a great question. So, it’s an excellent question. So, the only thing I would say semantically is, right, in my head, CAR T cells are not transplants per se, because I’m not changing the bone marrow. So, I would transplant a stem cell transplantation, separate from CAR T.   

Why do CAR T cells stop working? So, the short answer is we can speculate. We don’t know for sure for any individual patient. Three different buckets are involved. Three different things can happen. One, the T cells can stop working or disappear from circulation. So, that’s possible. CAR T cells don’t last forever. That’s actually okay, right? People often wonder like, “Man, I wish the CAR  
T cells could last forever.” I don’t know that I’d want that because as I alluded to, for as long as the CAR T cells are there, patients are immunocompromised, and so that can certainly interfere with the quality of life.  

So, it’s not necessarily true that the CAR T cells need to be there forever, but if they’re not there, or if they’re exhausted, which is actually a true scientific word for them not being able to activate and kill that cell when they recognized a protein, the BCMA, that’s one problem.  

The second problem is the myeloma cells can mutate. I alluded to this briefly earlier, where the cells can learn to shut off the protein, BCMA, or they can mutate the protein in just a way that the CAR T is no longer able to bind.  

And the third is something called the tumor microenvironment. And this is a little bit more complicated, kind of a grab bag of different things here. The idea is that myeloma cells have a lot of tricks, and they can use all of the cells around them to make it hard for the CAR T cells to get in, to get into the bone marrow and kill them all. And the T cells can be shut off before they even get there.  

So, it’s one of those three things in general. Which one is it for an individual patient? Hard to say. And so hopefully in the future, we’ll have better diagnostic tests to be able to identify who is a patient where another BCMA targeted therapy would work well versus, “Oh no, these myeloma cells are no longer expressing BCMA, let’s move on to a different target like GPRC5D.” We’re not there yet. We’ll get there hopefully in a couple of years, is my goal.  

Then, you know, Jennifer, that’s a good question. Well, can we do a second CAR T? And that’s very practical. What I would say is if the first CAR T therapy did what we expected it to do, if it lasted for as many years as I would expect for Abecma, that’s typically 12 to 18 months. For Carvykti, that’s typically over 24 months.  

If it worked and then it stopped working, and then probably the T-cells are long gone, it’s reasonable to try CAR T therapy again. In general, I would recommend, I strongly recommend a different CAR T-cell therapy, even if it’s targeting the same class, like BCMA, it’s going from Abecma to Carvykti or vice versa. 

The risk with giving the same CAR T-cell product again is that even though the T cells are a patient’s own T cells, the protein is slightly foreign. Abecma was derived from decades of mouse research. Carvykti was made from decades of llama research, believe it or not. Again, there’s no mouse or llama involved with the actual products nowadays, but in making the sequence years ago that came to them, they are foreign. There are foreign sequences on them, and so everyone’s host immune system eventually recognizes these cells as foreign.  

And so if you were to give the exact same product again, immediately the body would reject it the second time around, because it recognizes them and has learned to recognize it as foreign. But changing to a different CAR T cell is very reasonable. 

And again, for these newer GPRC5D targeted CAR T cells that, again, don’t target BCMA the way that Abecma, ide-cel or cilta-cel, Carvykti do, but target a different protein entirely, for those patients generally there’s no restriction on whether they’d received a prior CAR T cells. Ideally, it should be at least several months away, at least like a year or so, but if that’s happened and they stopped working, very reasonable. In fact, some of the trials actually require that patients going on to the study of a GPRC5D product have had a prior BCMA therapy of some sort before, and so they’re kind of built into the architecture of things. So, I think it’s very reasonable.  

Obviously, there are some unknown unknowns, right? What do you do if the T cells are being manipulated twice, so to speak. Patients ask me about that. I will say just to put that fear to rest, in general, by the time that someone’s had myeloma come back after the first CAR T cells, I alluded to this, the CAR T cells are long gone. So, there’s nothing left. But again, every case is different, and future research will help us kind of figure out how best to do this. 

Katherine Banwell:

Yes. We have one more question from Rita. She wants to know if there is an age limit on CAR T-cell therapy. 

Dr. Rahul Banerjee:

It’s a brilliant question. So, in brief, no. It’s a short answer. My oldest patient who got the CAR T is in their 80s and handled it across all my years at UCSF and here at Fred Hutch. More important than chronological age is physiologic age in terms of how robust they are, how robust they feel in terms of going through this. What I recommend, I’ve heard of centers that do CAR T therapy for patients in their 90s, for example. So, I think it’s not so much age, it’s how fit they are. 

Fit is easy for me to say. What does that actually mean? Typically it’s a combination of, you know, like cognitively, how are people doing? Because obviously if someone has baseline dementia, which is pretty uncommon, for example, maybe CAR T is not the best use of their time. The biggest thing that I think gets some of my older patients in trouble is frailty.  

So, just not being as fit as they were before in terms of muscle strength, being able to move around quickly, and so forth, or cardiovascular issues. Because it’s worth noting that with CAR T therapies that we have now, probably 60, 70 percent of patients will get CRS, cytokine release syndrome. So, that’s fevers and low blood pressure, that’s what I said earlier.  

But if you think about it, a fever of 104 degrees Fahrenheit, your heart rate’s going to be like 130, 140 beats per minute, beating very fast for several hours, sometimes longer than that. If you’re having low blood pressure, it’s your heart that has to push blood to overcome that low blood pressure. Can someone’s heart handle that level of stress? As people get older, that obviously gets harder.  

So, if someone is already just 75 and were being considered for CAR T therapy, certainly I think it’s very reasonable to talk about it. I would ask someone where I may have them meet with a cardiologist beforehand, possibly a geriatrician as well beforehand, just to see how can we optimize their health to make CAR T as safe as possible for them? So, it’s definitely possible. 

Katherine Banwell:

Well, thank you for that, Dr. Banerjee. And those were all great questions. If you have more as part of the audience, please continue to send them to question@powerfulpatients.org, and we’ll work to get them answered on future programs.  

Dr. Rahul Banerjee:

Absolutely. 

Katherine Banwell:

Well, Dr. Banerjee, we learned that the field of myeloma care and CAR T-cell therapy is advancing quickly. As we close out the program, what are you excited about? Why are you hopeful? 

Dr. Rahul Banerjee:

Absolutely. So, I think I’m excited because, especially for CAR T therapy in particular, at our center, for example, we used to only be able to do like one or two patients per month. It was a very steady, low stream, because there were a lot of issues with manufacturing, and it was during the COVID pandemic, and there were supply chain issues, et cetera. 

And there were studies, and I remember them, very dark studies in 2021, 2022 even, that patients were more likely to die on the  
CAR T waitlist than they were to actually get CAR T therapy. That’s terrible. And we’ve come a long way since there, where our capacity, every year we’re doing more and more patients to CAR T therapy per month, which is wonderful. 

And so what I would say is that makes me hopeful, right? Because CAR T therapy, I’m not saying that everyone is required to get CAR T therapy. I have plenty of patients who hear about it and are like, oh, no thanks. I’d rather stay with what I’m getting right now with my local oncologist. And that’s okay, but I want it to be an option for as many patients as possible, and I think we’re making strides there. 

And so I think what I would say, the kind of closing words here is, we only can get you CAR T therapy if we know about your case and if you know about us. And so what I would say, I’m sure to people listening to this, you’re very motivated. And so you know the importance of having a myeloma specialist in your field. 

What I would say is my patients who do the best are the ones who are co-managed. They have a doc out in the community. I have patients from Idaho, Montana, Alaska, Eastern Washington, et cetera. They have an oncologist who knows them well, who knows their community well, easy to get to, can handle everything. They’re a jack of all trades and very good at it. And then they have me, who they see periodically for CAR T evaluation, just discussions about CAR T by telehealth, something along those lines. 

And I’m able to talk about CAR T therapy in detail and answer their questions. And so what I would say is, I’m hopeful that that trend will continue, and that if someone’s even interested in hearing about CAR T therapy, they don’t meet me for the first time when they actually need CAR T therapy right then and there. They meet me years beforehand to just talk about CAR T, so they know it’s an option for them. 

And that time – because we don’t have as long of a wait list as we do, and we used to do, if and when the time comes that we all talk, me, the patient, the caregiver, and the primary oncologist, and say, “Look, I think now is time,” we’re able to make it happen. 

Katherine Banwell:

Yes. That’s a promising outlook to leave our audience with, Dr. Banerjee. Thank you so much for joining us today. 

Dr. Rahul Banerjee:

Absolutely. The pleasure was all mine. Looking forward to seeing many of you on a future episode of this. 

Katherine Banwell:

And thank you to all of our collaborators. To learn more about CAR T-cell therapy and to access tools to help you become a proactive patient, visit powerfulpatients.org.  

I’m Katherine Banwell.

Thanks so much for being with us today.  

Follicular Lymphoma Expert Q&A: Coping with Relapse and Managing Treatment Side Effects

Follicular lymphoma expert Dr. Kami Maddocks from The Ohio State University Comprehensive Cancer Center empowers patients and families with practical guidance on key aspects of managing follicular lymphoma. Dr. Maddocks covers effective strategies for managing treatment side effects, navigating the challenges of relapsed or refractory disease, and defining what survivorship means for both patients and their care partners.

Download Guide | Descargar Guía

See More from START HERE Follicular Lymphoma

Related Resources:

How Do Outcomes for Relapsed/Refractory Follicular Lymphoma Vary?

How Do Outcomes for Relapsed/Refractory Follicular Lymphoma Vary?

Addressing Vulnerabilities in Follicular Lymphoma

Addressing Vulnerabilities in Follicular Lymphoma

What Are Common Follicular Lymphoma Treatment Side Effects?

What Are Common Follicular Lymphoma Treatment Side Effects?


Transcript:

Lisa Hatfield:

Welcome to this START HERE Patient Empowerment Network program. This program bridges the expert and patient voice, enabling patients and care partners to feel comfortable asking questions of their healthcare team. I’m Lisa Hatfield, a cancer survivor and also an Empowerment Lead at Patient Empowerment Network. Joining me today is hematologist-oncologist

Dr. Kami Maddocks, Professor of Clinical Internal Medicine in the Division of Hematology at The Ohio State University Wexner Medical Center. Dr. Maddocks specializes in treating patients with B-cell malignancies, including non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, and chronic lymphocytic leukemia. Dr. Maddocks researches new therapies for these hematologic malignancies, largely through evaluating new targeted therapies in clinical trials. Thank you so much for joining us, Dr. Maddocks.

Dr. Kami Maddocks:

Thank you, Lisa. It’s a real pleasure to be here with everyone today and talking about follicular lymphoma, and I just really appreciate you having me.

Lisa Hatfield:

The world is complicated, but understanding your follicular lymphoma diagnosis and treatment options along your journey doesn’t have to be. The goal of START HERE is to create actionable pathways for getting the most out of your follicular lymphoma treatment and survivorship. Joining us are patients and care partners facing a follicular lymphoma diagnosis, some of which are newly diagnosed, in active treatment, watch and wait, and also living for years with their disease.

START HERE is designed to provide easy-to-understand, reliable, and digestible information to help you make informed decisions. I’m thrilled you’ve joined us. Please remember to download the program resource guide via the QR code. There is great information there that will be useful during this program and after. Okay, Dr. Maddocks, let’s start here. What is the latest in follicular lymphoma, and what are the most important highlights for patients and families?

Dr. Kami Maddocks:

When we look at some of the stuff that’s changed in follicular lymphoma, there has actually been some really exciting developments just in the last year in follicular lymphoma. So when you look at patients who have relapsed or refractory follicular lymphoma, we’ve actually seen the approval of three different new therapies just in the last year for relapsed/refractory follicular lymphoma. So one of those therapies, we saw a brand new approval, and that’s a therapy which combines an oral targeted therapy with a monoclonal antibody.

So the combination of the CD20 antibody, obinutuzumab (Gazyva), in combination with the BTK inhibitor zanubrutinib (Brukinsa) was approved in March of 2024 for patients with relapsed/refractory follicular lymphoma. And this was based on a study that compared that to the single agent anti-CD20 antibody. So while we have had CD20 antibodies approved in both original treatment for follicular lymphoma and relapsed disease, it was the first time that we’ve had a BTK inhibitor approved for the treatment of relapsed/refractory follicular lymphoma.

In May of 2024, we saw the approval of actually the third chimeric antigen receptor T cell or CAR T-cell therapy for relapsed/refractory follicular lymphoma. So previously, we’ve had two different CAR Ts that target the same antigen or protein CD19 on the cell. And the third therapy with the same target was approved in May of this year for relapsed/refractory follicular lymphoma. And then in June of 2024, we actually saw the approval of the second bispecific antibody for the treatment of relapsed and refractory follicular lymphoma.

So previously, we had one approved almost two years ago in December, and a second one, epcoritamab-bysp (Epkinly) was approved in June of this year for patients with relapsed/refractory follicular lymphoma. So three different treatments approved in this setting in the last year, which increases the options for patients. It also provides us with thinking about sequencing these agents. And there’s a lot of studies ongoing to decide or to think about what is the best way to sequence therapy, because there’s no right or wrong answer currently in which therapy did you choose and when in patients with relapsed/refractory follicular lymphoma.

And then thinking about managing when we’re choosing these therapies, what are the side effects of these therapies and managing these side effects? Right? Because chemotherapy is often used for patients with initial diagnosis, and there is very specific side effects to chemotherapy and ways to manage those side effects. But when we look at some of these newer therapies, we have to think about the different toxicity profiles that they have and how we manage those toxicities.

So when we’re thinking about the newer therapies, like bispecific antibodies and CAR T-cell therapies, there’s very specific toxicity with those therapies, including cytokine release or CRS. And then something called ICANS, which is immune effector cell-associated neurologic toxicities, which are neuro side effects of these therapies. And so how do we identify and manage those therapies and now even looking at ways to potentially prevent patients from having those specific toxicities.

Lisa Hatfield:

Okay, thank you. So regarding those toxicities, like the ICANS and the CRS, is there a difference in how you treat patients? For example, if a patient might experience those side effects, are they hospitalized for that type of treatment initially, or are all of these new treatments done on an outpatient basis?

Dr. Kami Maddocks:

Yeah, that’s a great question. So the answer can be variable depending on the specific product or the center where the patient’s receiving them, and then even the disease that they’re used in. So let’s just talk about bispecific antibodies to start. So the first bispecific antibody that was approved in follicular lymphoma was mosunetuzumab-axgb (Lunsumio). There’s no required hospitalization to administer that, but there is a recommendation that if patients have signs or symptoms of cytokine release.

So the primary symptom is fever. That’s the number one most common symptom that patients will get and how we define cytokine release. But patients can also have hypoxia or a drop in the oxygen or hypotension and a drop in their blood pressure. So if they have these, it’s generally recommended that they’re admitted for a period of observation to ensure that those toxicities don’t worsen or escalate and that they’re treated if they do.

Which treatment can include ruling out other causes. Some patients may need antibiotics if they have low blood counts and a fever. Some people will need fluids and oxygen. Then sometimes we use steroids like dexamethasone (Decadron) or even cytokine blockers to help manage those side effects, particularly if they’re what we call higher grade or more significant. The second bispecific antibody epcoritamab-bysp. That was previously approved in diffuse large B-cell lymphoma and there was a recommended hospitalization with a step-up dosing for that.

However, in follicular lymphoma, when they studied that, they gave an extra dose. So part of trying to prevent the cytokine release is giving a lower dose and then increasing the dose each week until you reach the maximum dose. So they added an extra kind of intermediate dosing in the follicular dosing and showed that that made a lower risk of…a lower number of patients had cytokine release. And that the majority of them had the lowest grade cytokine release.

So in follicular lymphoma, it’s actually with that increased one dose in there to get to the maximum dose. It’s actually not recommended, or it’s not required that patients are hospitalized for any of the doses. But, of course, if they would, same thing, if they would have side effects, then you would consider that. And then the same thing could be said for the CAR T-cell therapies. Some of them are given inpatient and then patients are monitored for a period of time, and then some are administered as an outpatient. And patients are seen daily for that to check on how they’re doing, monitor for side effects, have labs. And sometimes it just depends on the center administering the therapy, how they have a setup for patients to be monitored.

Lisa Hatfield:

So I have two follow-up questions to that overview. Are these newer approved therapies, are they available at some of the smaller cancer centers, or are they only available right now at the larger cancer centers or academic centers? Then my second question is, are they limited duration therapies or like bispecific antibodies, does that just continue until disease progression?

Dr. Kami Maddocks:

Yeah, those are great questions. So in general, if you look at the combination of the obinutuzumab and zanubrutinib that should be able to be administered anywhere, the therapy for the oral therapy is continued until progression. If you look at the bispecific antibodies, there’s both. There’s a time-limited therapy, and then there’s one continued until progression. I think in general, we’ve seen that initially these have been used at larger treatment centers, but now that they’ve been approved for a while, we have seen a lot of these being used at smaller cancer centers and in the community centers. Sometimes patients may receive their initial dosing at a larger center and then transition to a local center. But I think, like I said, now, especially the one that’s been approved for a while, we’re seeing that it can be started at many places.

Lisa Hatfield:

Thank you so much for that important overview, Dr. Maddocks. All right, it’s that time where we answer questions we’ve received from you. Remember, as patients, we should always feel empowered to ask our healthcare providers any and all questions we might have about our treatment and prognosis. Please remember, however, this program is not a substitute for medical care. Always consult with your own medical team. So before we dive into this Q&A, since this program centers on coping with relapse and managing treatment side effects, how do you approach these first-time conversations with patients and their care partners who are facing relapse and potentially dealing with a new set of side effects due to the changes in their treatment regimen?

Dr. Kami Maddocks:

I think that’s a great question, and I think there are a lot of things to consider. So I think the first thing that we want to think about when we’re talking about patients having relapsed or refractory follicular lymphoma is that just because patients have relapsed or refractory follicular lymphoma doesn’t always mean that they need treatment. So many patients, when they’re initially diagnosed with follicular lymphoma, are going to go through a period of observation or watch and wait where we know that they have follicular lymphoma, but they don’t have symptoms of their disease.

They don’t have a large number of lymph nodes involved, or their lymph nodes are not very large by the scans, and they don’t necessarily need to be treated until they become symptomatic or have certain concerns from their lymphoma that’s causing problems. So the same thing can happen probably more with relapse than necessarily refractory disease, but patients may…you may detect on scans that they have lymph nodes that are growing or that their disease has recurred, but they don’t always necessarily need to receive treatment.

Once you’ve identified that, yes, a patient requires treatment for their relapsed or refractory follicular lymphoma, the next thing to think about is that patient and their disease. So what age is the patient? What were they treated with initially? Because not all patients receive the same initial therapy. So the decision about what they’re going to receive when they relapse is going to be somewhat dependent on what they received for their initial therapy, what side effects they had from that therapy, and how they responded to that therapy.

The next thing is going to be that there is not just one option at relapse so really discussing the different options for those specific patients, and what are the options, what are the side effects of those options, what is the treatment schedule of those options? Because some treatments may have more toxicity, but they’re time-limited, whereas other therapies may be continued to help progression, they may have less toxicity, but over time that’s a toxicity that patients continue to experience on a daily basis.

So really talking to the patient about the options, what does the schedule of that treatment look like? Do they have to come in weekly? Do they have to come in once a month? And then again, the side effects and how that fits into side effects that they had with their initial therapy, how they tolerate that, are any of those side effects still there?  For example, if a patient has neuropathy from their therapy, that might be something that lasts and then considering all those things and making an informed decision with the patient.

Lisa Hatfield:

Okay, thank you. And these questions are in the perfect order, because we have a question from Lauren asking you, what is the difference between relapsed and refractory? 

Dr. Kami Maddocks:

Okay, this is another great question. I’m sure all these questions are great. When we think of relapsed disease, we think of a patient who’s had therapy, got in a response to that therapy, that response has lasted some time, and then their disease recurs. When we think of refractory, we think of that more as patients that have received a therapy, and they haven’t responded. Now, there is no standard definition of refractory. So we all agree that if a patient gets a treatment and their disease does not respond to that treatment, they’re refractory to that treatment.

But there’s no defined time for which if a patient has a treatment and responds to that treatment but has a short relapse, what’s really considered refractory. In general, a lot of studies that look at a therapy say that if you’ve had it, like if you’ve had rituximab (Rituxan) and you’ve relapsed within a six-month time frame, that that’s refractory. But some studies use three months instead of six months.

Lisa Hatfield:

Okay, thank you. Another patient, Jeff, is asking, Dr. Maddocks, I’m currently in an observation stage of non-Hodgkin lymphoma. I get blood work twice a year and scans once a year. I’m hoping it stays slow-growing. How long on average can a person live in observation mode before treatment must occur?

Dr. Kami Maddocks:

So this is another great question. And I’m going to provide kind of an overview that we’ll kind of set up, because there may be more questions like this. But in general follicular lymphoma is not one disease, which I’m sure since this is a program focused on relapsed/refractory follicular lymphoma, a lot of patients have heard this and know this. But it’s what we call it’s very heterogeneous, or it can behave very differently in patients, meaning that some patients will have very indolent disease, and then there’s a small portion of patients whose disease will be more aggressive.

We know that when we diagnose patients with follicular lymphoma there are some patients that are diagnosed and require treatment pretty quickly, whereas there are other patients that go many years, many, many years without requiring treatment. Some of that is because of the disease, and some of that is because of how we find a patient’s follicular lymphoma. Some patients, we don’t find it until they present with symptoms. Some patients find their own lymph nodes, and some patients are diagnosed because they have a baseline scan that for a totally different reason, maybe get into a car accident, have scans to make sure nothing’s broken, you find an enlarged lymph node, you biopsy it, and you find this diagnosis.

All that said, there are some studies that have looked at patients who are on observation or watch and wait and looked at treating patients who have what we call low tumor burden, or not a lot of lymph nodes, or not very large lymph nodes, but have what’s called advanced stage disease. So lymph nodes on both sides of the diaphragm, not large enough to necessarily require more aggressive treatment, they don’t have symptoms. But we’ve treated, we’ve looked at studies treating those patients with observation or watch and wait or single agent rituximab (Rituxan) therapy. And when you look at the patients in those trials, the median time to needing treatment for patients from observation was three years.

However, there were 30 percent of patients, so one out of three patients who were still being observed at 10 years without requiring any therapy. So there are patients, that’s almost a third of patients at 10 years who’ve been observed, not required therapy in that population of patients. And certainly I have been practicing for a while where I’ve seen patients, I do have some patients who’ve gone longer than that without needing therapy.

Lisa Hatfield:

Okay, thank you. And there you go, Jeff, we hope that you’re in that third. 

Okay, thank you for explaining that. Next question, I’m not sure if it’s Jeff Run or Jeffrey is asking about the most common side effects that are associated with bispecific antibodies, and what precautions can be taken to reduce the risk of infection?

Dr. Kami Maddocks:

Yeah, another great question. There are two different bispecific antibodies that are now approved for relapsed/refractory follicular lymphoma. And I will take this time to also say that some of the exciting ongoing work is looking at those agents in clinical trials, in the frontline setting, in combination with other therapies particularly non chemotherapies.In general, I would say similar side effect profile. The most common side effect between them is the cytokine release or the CRS. So that is the most common side effect. Again, this can be defined in different ways. The most common side effects that you see from that define CRS are fever, hypotension or low blood pressure, hypoxia or low oxygen, shortness of breath, chills, tachycardia or higher heart rate. 

We have talked a lot about CRS and what it entails and how it is defined and presents. But management, it depends on what we call grading. So for patients who just, who have a fever, oftentimes, number one, you want to make sure that it is CRS and that there’s not an underlying cause. So ruling out infection or coexisting infection, if a patient is neutropenic or has a low neutrophil count and is at high risk for infection, you may treat them with antibiotics with a fever while you rule out infection.

But oftentimes, if they have a fever, you can manage symptomatically anti-fever medications like acetaminophen (Tylenol). If a patient has worsening CRS and has other symptoms associated with it, such as the hypoxia, low oxygen, or hypotension, low blood pressure, then that’s when we escalate therapy. So one you direct treatment towards that. So if they need fluid, if they need oxygen, but then that’s when you’re thinking about starting medications such as the steroid medication. So we give intravenous dexamethasone, or there are certain cytokine blockers such as tocilizumab (Actemra) that can be given to help treat the side effects of the cytokine release.

Other common side effects or that we’re seeing in more patients in the clinical trials, fatigue, rash, and then infections including upper respiratory infections, and then COVID-19 infection as well. So part of treatment of these side effects is early recognition of the side effects. So patients are monitored closely and that you’re dealing with the side effects to help them from worsening. I think infection prevention is very important with these. So it’s recommended to consider prophylaxis for certain infections. So antiviral medication to prevent viral, such as shingles reactivation, medication to prevent a specific type of pneumonia, PJP pneumonia, and then consideration I think of just making sure that patients are up to date on vaccination. And if patients do have infection while they’re getting treated, potentially delaying treatment or taking a break in order for them to recover from treatment.

Lisa Hatfield:

Okay, thank you. And this person did not give their name but is asking, Dr. Maddocks, I wanted to know how to travel as safely as possible. Is it advisable to get certain vaccines for travel like yellow fever? I plan to travel to Europe via plane and cruise. They say that there’s stage III non-Hodgkin’s follicular lymphoma getting treatment every eight weeks.

Dr. Kami Maddocks:

So this is a great question, and I’m probably going to answer this a little bit more generically, because I think that it can depend a little bit as far as what specific vaccines. But when thinking about travel, I think that it’s a good idea to look at where you’re traveling because both, where you’re traveling time of year you’re traveling and what you’re going to do when you’re somewhere can depend on what vaccines are recommended. I usually advise patients to consider looking at the CDC guidelines for recommendations for what should be received in that area, travel that time of year, what they’re going to be doing.

And then sometimes there are places that will actually have a travel clinic. Once I know what vaccines are recommended, the patient knows what vaccines are recommended, then I usually work with them and pharmacy to decide what vaccines, if they can receive all those vaccines or if there were certain ones that we may not recommend. In general, it can depend on a patient, what treatments they’ve received or if they’re actively receiving treatments. But in general, we like to avoid live virus vaccines in our patients. So I take into all those factors and then would recommend discussing the specifics with your physician.

Lisa Hatfield:

Luca is asking what are the long-term side effects of bispecific antibody treatment, and how will I be monitored for them after treatment ends?

Dr. Kami Maddocks:

So another great question. I think, when we think about the side effects in general, the bispecific antibodies in the CAR T both have those unique toxicity, cytokine release being the most common. And then you also have worry about the neurological toxicity. The difference is that, depending on the specific, bispecific or CAR T that you use, but we usually, typically see these occur in lower grade or not as severe with a bispecific antibody than you can see with a CAR T-cell therapy.

You can still have cytopenias and infection risk with these therapies. Whereas in chemotherapy, we think of that as more generalized toxicities, with the cytopenias, with the risk of infection with the GI toxicities. When we think about long-term side effects, so I think one of the important things to recognize is that bispecific antibodies have not been around that long in the scheme of things, though we can’t say, the risk of 20 years, what do we see or even 10 years.

But when we think about what we have seen, we’ve seen things like the cytokine release, the infections, the cytopenias, but what we haven’t seen is things like the secondary malignancies that we worry about when we think about chemotherapy or even maybe immunomodulatory therapy or secondary cancers that patients can develop. I think for long-term monitoring, right now, at least the biggest thing you want to think about is that these therapies do deplete the lymphocytes, for a prolonged time. And so the risk of viral infections or reactivation of infections, and making sure that’s being considered.

Lisa Hatfield:

Okay, thank you. That’s an important question. So another may possibly be a care partner, Marilyn. How can I best support my loved one during relapse and what should I do if I notice my husband with new or worsening symptoms?

Dr. Kami Maddocks:

So another great question. I think it’s first of all important to ask the physician about what symptoms to watch for. So you know, are there certain worsening new symptoms or worsening symptoms that seem more likely to be related to follicular lymphoma versus something else. I think it’s always important to encourage your loved one if they are experiencing new symptoms to reach out to the physician so that they can be evaluated. Because follicular lymphoma is a disease that many people live with and many people live with it for many years. We know that patients can experience other things.

Not everything is going to be just because of the follicular lymphoma. So it’s important to be evaluated, and recognize what is going on and what is attributed to the follicular lymphoma. I think being supportive, thinking of questions to ask and making sure that those questions are answered. I think thinking about, are there resources available? I think educating yourself is one of the most important things that people can do. So knowledge is power. So just participating in things like this I think can be very helpful, because learning about what’s out there, knowing that there are many options, I think being supportive and having a positive attitude, are all helpful things.

Lisa Hatfield:

Okay, thank you. So we have another big and important question from Aubrey. How can I live a full life with follicular lymphoma while managing the emotional toll of knowing the disease may relapse? And what lifestyle changes or habits should I focus on to maintain my health during remission?

Dr. Kami Maddocks:

Yeah, so this is another great question, and I think there’s probably lots of different ways to answer this or lots of different things to consider. So I think in general, as we’ve talked about follicular lymphoma is something that people live with for a long time. So thinking about just your general health and general disposition. So, we want to think about incorporating exercise, incorporating a healthy lifestyle, thinking about exercise, and being physically active.

Thinking about particularly diet and not saying that there’s any food that you need to avoid or any specific thing, but I think eating healthy is important. I think sleep hygiene is, can be very critical for patients. I think finding, and then just general health, it’s good to have a PCP so that you’re getting good routine health maintenance. We have to think about making sure that we’re managing other medical things like blood pressure, glucose, looking, doing other routine cancer screenings, depending, if somebody’s male or female, but the screening that’s recommended for that.

Now when we’re thinking about managing this does take an emotional toll because a lot of times, when somebody’s initially diagnosed, if they don’t need treatment, the question is always like, well, how long am I, is it going to be before I’m going to need treatment? How am I going to tolerate that treatment? How long is that treatment going to last? And then that resets once a patient’s had treatment. Well, how long will I stay in remission for this treatment? What’s going to be next?

I think things that can help with that are, sometimes I think involving like psychosocial oncology, I think support groups, I think that it’s very beneficial for many patients to talk to people, whether it be through a u look at the median age at diagnosis is in the 60s, and median overall survival is greater than 20 years. So many patients are going to live with this more like a chronic disease. And so learning to kind of knowing basic facts on what it is, what are the treatments that are available, what do those treatments look like, what are the reasons that you need those treatments? And that you are able many times in those periods of not needing treatment to live a very normal lifestyle and do things. I think making sure that, I think it’s important.

One thing that I think can be helpful is you’ll continuously follow up with your physician. So thinking about questions and concerns that you have throughout the period of time, writing them down that gets them out of your mind on paper. And then when you go to see your doctor next, you have that list of questions. Because I think, sometimes we think about things, and then we worry, worry, worry. But putting them down on paper or even sending them through like a secure MyChart email message and then talking them out, because a lot of times if you don’t do that, then when you go to see your physician you think, oh, I don’t really have any questions.

And then you leave and you’re like, oh, I should have asked these 10 different things. So again, I think asking for resources. So there are many different patient friendly resources out there. I think reading material that’s been written or vetted by medical professionals as opposed to just any random material can be very helpful for patients. And then again sometimes seeking out kind of peer support.

Lisa Hatfield:

Okay, great, thank you. Sean is saying that he was diagnosed with follicular lymphoma in 2022 and in an active treatment. What advice do you have for someone transitioning from patient to survivor? I am eager and fearful.

Dr. Kami Maddocks:

Awww. Well, another good question. And I think one thing I want to recognize is that somebody with cancer is defined as a survivor from the time they’re diagnosed moving forward. So you’re already a survivor. But when you, I do think, and I tell patients this, even when we’re talking about starting treatment, I do think that being aware of kind of where patients are at mentally is important.

Because when you go through, when a patient goes through treatment, they’re very focused on next steps and next steps when you’re going through treatment are, when’s my next treatment going to happen? When’s my next scan going to happen? When you get to that point, when you’re done with treatment, you no longer have those small milestones that you’re reaching the next treatment, the next scan. You now are like, oh my gosh, I had this treatment and now, how long is it going to last?

What’s going to happen to me? What else can happen to me? And there can be a lot of fear and anxiety. I would first tell you that’s totally normal. That is a normal feeling to have at this point. So I think one, recognizing that you have them is important. I think considering things like we’ve talked about, is there a survivorship clinic, is there psychosocial oncology? Is there something that might help in talking those things out? I think setting up milestones, what is the next thing? I’m going to have a three-month appointment, I’m going to have labs.

These are the things I need to be thinking about, but if I’m not noticing these also, what things can I do to return to the things I like to do. I think also I would go back to saying, I think this is where just thinking about getting good sleep, getting exercise, eating a healthy, balanced diet, and then socializing and making sure that you’re involving friends and family.

Lisa Hatfield:

Okay. Thank you. And, Sean, you’re already a survivor, Dr. Maddocks said so. So good luck, Sean. All right, Dr. Maddocks, thank you so much for being part of this Patient Empowerment Network START HERE program. It’s these conversations that help patients truly empower themselves along their treatment journey. On behalf of patients like myself and those watching, thank you so much for joining us, Dr. Maddocks.

Dr. Kami Maddocks:

Well, Lisa, thank you so much for having me. It’s been a real pleasure, and I hope everybody has a great day.

Lisa Hatfield:  

Thank you. I’m Lisa Hatfield. Thank you for joining this Patient Empowerment Network program.


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Overall Health and CAR T-Cell Therapy | Tips for Preparation and Recovery

 

How can you best prepare to undergo CAR T-cell therapy to aid in optimal recovery? This animated explainer video provides key advice for learning about CAR T-cell therapy, consulting with your care team members, and tips for recuperating after the process. 

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Current and Emerging CAR T-Cell Therapies for Myeloma

CAR T-Cell Therapy | Key Considerations for Myeloma Patients

CAR T-Cell Therapy | Key Considerations for Myeloma Patients

Transcript:

CAR T-cell therapy offers a groundbreaking approach for people living with myeloma, and taking steps to optimize your health can play a crucial role in your treatment journey. From preparing your body and mind before therapy to focusing on recovery afterward, there are actionable ways to support your overall well-being and, potentially, enhance outcomes. 

Here are some key steps to boosting your overall health when preparing to undergo CAR T-cell therapy: 

Start by learning about CAR T-cell therapy.

Take the time to understand how the treatment works and what to expect. Your care team can guide you through the process, from the collection of T cells to potential side effects and what to expect following therapy. Educational resources like those found on the Patient Empowerment Network website can also empower you with knowledge and confidence.  

Next, consider cost.

Confirm insurance coverage and make sure you understand the financial impact of CAR T-cell therapy. You can also meet with a financial counselor or a navigator at your medical center to see if there are any resources to assist with paying for therapy. 

Then, consult with your CAR T-cell therapy team.

When undergoing pre-treatment evaluation, be sure to get all of your questions answered and to understand what support will be available to you during the CAR T-cell therapy process.  

You should also build a support system.

Having a family member or friend who can accompany you to appointments and assist with your recovery is vital, and often required by the CAR T-cell therapy center. A care partner can be an advocate for you and help to ensure you feel supported throughout the process. 

It’s also important to plan ahead.

Coordinate with your employer for the time you’ll need to take off from work. And, if necessary, arrange for child or pet care so that you won’t have to worry about these logistics following treatment.  

And, last but not least, meet with other care team members:  

Consider a consultation with a nutritionist for advice on a diet that supports your body through the CAR T process, as well as safe handling tips for meals following treatment.  

A social worker can help you manage the emotional, logistical, and financial aspects of CAR T-cell therapy.   

And, meeting with a pharmacist may also be useful, as they can provide specific information about medications you will take before, during, and after treatment.  

After CAR T-cell therapy, maintaining your health is essential to boost recovery and to reduce potential side effects or complications. Here are some useful tips to aid in recovery: 

Focus on Nutrition.

Your body will need extra support as it heals. A balanced diet rich in vitamins and minerals can help boost your immune system.  

Stay Active.

Light exercise, such as walking or yoga, can help improve your strength and mental well-being. Consult with your doctor before starting any exercise routine.  

Monitor Your Mental Health.

Emotional health is just as important as physical health during recovery. Reach out for support if you’re feeling overwhelmed or anxious.  

Stay on Top of Follow-Up Appointments.

After therapy, your healthcare team will monitor your progress. Attend all follow-up appointments and keep track of your symptoms. If you notice anything unusual, contact your doctor immediately.  

CAR T-cell therapy is a powerful treatment and taking steps to prepare and care for yourself can make a significant difference in your recovery.

For more information and additional resources, visit powerfulpatients.org.

What Are Common Follicular Lymphoma Treatment Side Effects?

What might follicular lymphoma patients experience for treatment side effects? Expert Dr. Brad Kahl from Washington University School of Medicine discusses common treatment side effects that patients might experience, some methods for dealing with side effects, and other precautions to help ensure optimal patient care. 

Download Resource Guide | Descargar Guía

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Why Does Follicular Lymphoma Relapse for Some Patients?


Transcript:

Lisa Hatfield:

What are the common side effects of the recommended treatments in newer therapies? And a really important question. Are there long-term side effects that I should be aware of or that a patient should be aware of?

Dr. Brad Kahl:

Yeah, the side effects are going to be different for all the different new agents that I mentioned. With the bispecific monoclonal antibodies, there’s a little bit of risk for something called cytokine release syndrome. When you’re first starting on the drug, sometimes the drugs are really potent at activating the patient’s immune system. And as that immune system is getting revved up, the immune system will release chemicals or cytokines, which can give you fevers and make you feel like you have the flu. It’s just your immune system responding.

And so that’s something that we have to watch for as we’re starting a bispecific, that’s usually a short-term problem. And it’s usually pretty easily managed with steroids or other drugs that can tamp down the immune system. And then once you’re past that risk for cytokine release syndrome, the bispecifics usually go pretty smooth, but the bispecifics do deplete your body of healthy B cells in addition to the follicular lymphoma cells.

So they do weaken the patient’s immune system some, and I’d say that’s the biggest risk that we have to worry about in patients getting a lot of these different treatments is just what it does to your immune system. And so we’re always telling patients to call us if you get a fever, infections in a patient on treatment can become a big deal. And that’s why we want those phone calls so we can figure out if you need to get seen, if you need to go to an emergency room, if we need to start on broad spectrum antibiotics immediately, if we need to bring in for fancy testing, because sometimes people can get kind of oddball or rare infections. 

So infections, infections, infections are the things we worry about the most with most of the treatments that we give to people with relapsed follicular lymphoma. That’s true of the CAR T-cell products, cytokine release syndrome. We also have to worry about some neurologic toxicity that can happen if that happens, that’s going to occur while the patient’s in the hospital with us getting those treatments. But again, these drugs will deplete the immune system for months and months, maybe even a year, maybe longer. So we have to just be super careful about infections in patients getting these different treatments that I mentioned today.


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Bispecific Antibody Therapy | Managing Side Effects

Bispecific Antibody Therapy | Managing Side Effects from Patient Empowerment Network on Vimeo.

What should myeloma bispecific antibody therapy patients know about managing side effects? Nurse practitioner Alexandra Distaso from Dana-Farber Cancer Institute discusses common short-term and long-term side effects, members of the healthcare team, medications for managing side effects, and how care partners can support bispecific antibody patients.

Alexandra Distaso, MSN, FNP-BC is on the Multiple Myeloma Nursing Team at Dana-Farber Cancer Institute.

See More from The Care Partner Toolkit: Bispecific Antibodies

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Bispecific Antibody Therapy Support | Care Team Members and Resources

Bispecific Antibody Therapy Support | Care Team Members and Resources

Transcript:

Katherine:

What are the short-term side effects associated with bispecific therapy?  

Alexandra:

Yeah. So, the short-term side effects that we’re watching for are these reactions in the hospital called CRS, cytokine release syndrome, and neurotoxicity.   

So, the CRS is an inflammatory response where cytokines are released and usually cause a fever. We monitor and make sure that the fever isn’t being caused by some sort of infectious process or there’s no other cause for the fever. And if not, then there are medications we can give to help reverse these side effects while you’re in the hospital. 

Katherine:

Who else is on the healthcare team when someone receives these therapies?  

Alexandra:

Yep. So, you’ll always meet with your oncologist or an oncologist at the academic medical center where you’re going to be getting the medication to go over potential side effects, what the treatment entails, and consent. We have nurses here that are specific to bispecific antibodies, that help coordinate with your local team if you’re going back to your local practice. We have the infusion nursing team who are the ones who are actually giving the bispecific antibody therapies. They explain kind of what to watch for at the site where the injection goes. And then we have pharmacists who are also available to meet with you and go over any questions you may have about the treatment.  

Katherine:

What do we know about long-term side effects? Are there any?  

Alexandra:

So, long term, what we’re really seeing is risk for infections. So, all of these medications lower your blood cell counts, and we have to watch for these opportunistic infections, fungal, bacterial, viral.  

Which is why it’s important that we have everyone on supportive medications to try and prevent that from happening. But long term, that is certainly something that we’re seeing. With the talquetamab, there can also be some skin and taste changes, and those are not necessarily right at the inpatient dosing, but we can see that. But those are things we’re also managing in the months after the initial therapy.   

Katherine:

Okay. Why is it so important that care partners let the healthcare team know of any changes that they see in their loved ones?  

Alexandra:

I say this to my patients and their families all the time. They know their family member best, and they may be one to notice that they’ve been more tired, or their energy just isn’t the same, or they do have a little cough that maybe the patient hasn’t even really noticed. And those are all things that we want your observation, we want you to speak up about, because the sooner we address some of these problems, the less complications the patients may have.  

Katherine:

What are the supportive medications for somebody who might be having side effects?  

Alexandra:

Yeah, so with the talquetamab (Talvey), which we’re primarily seeing a lot of skin side effects and mouth discomfort, a lot of the time we have special mouthwashes to prevent discomfort and irritation. Things like biotin to just keep the mouth moisturized. Steroid creams and nail ointments to help with sometimes some peeling of the skin.

And then for all bispecifics, we have everyone on viral prophylaxis. Something like acyclovir (Sitavig or Zovarax) or valacyclovir (Valtrex). PJP prophylaxis. So, something like sulfamethoxazole and trimethoprim (Bactrim) or dapsone (Aczone). And almost all of our patients are on an IVIG infusion once a month to help support their immune system and prevent against infections.  

Katherine:

Alexandra, you mentioned care partner looking for a cough, for instance, in a patient.  

What other things should care partners be looking for?  

Alexandra:

Any kind of change in the patient’s baseline is always helpful to know. So, if people are feeling much more tired, even if you’re not due for your therapy, sometimes calling to say that they just don’t seem themselves, we can check their blood counts. And again, sometimes they might need a blood transfusion, or their white count might be quite low, and they might need some Neupogen or filgrastim to help kind of support their blood counts. So, really kind of notifying us, even if it doesn’t seem like a big thing, it’s always better to call. 

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy from Patient Empowerment Network on Vimeo.

What are bispecific antibodies, and how are they advancing myeloma care? Dr. Omar Nadeem of Dana-Farber Cancer Institute discusses the role of this new therapy in myeloma care, shares an update on ongoing bispecific antibody research, and compares this treatment to CAR T-cell therapy.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

Download Resource Guide

See More from Evolve Myeloma

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What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

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Myeloma Research Highlights From ASH 2023 

What Should Myeloma Patients Ask About Developing Research

What Should Myeloma Patients Ask About Developing Research?

Transcript:

Katherine:

Well, another therapy that has emerged in myeloma is bispecific antibodies. What patient type is this therapy right for? 

Dr. Nadeem:

So, bispecific antibodies are great because they’re off the shelf. What that means is that CAR-T cells, we first have to collect the T cells and we then have to send them off to be manufactured, and that manufacturing process can take up to a month, sometimes even longer, for some of the current available CAR-T products.   

And then, after the cells are returned to the facility, we then give usually three days of chemotherapy to try to suppress some of the immune systems of the patients. So, that way, when the cells are administered, they can expand robustly and do essentially what they need to do. 

So, that whole logistical process can take a couple of months by the time you identify somebody for CAR-T cells and then, from that moment until they can actually be treated. With bispecific antibodies, if we think somebody’s ready to go, you can basically get it as soon as we can have somebody ready to go either in our clinic or on the in-patient facility.

So, they’re much easier. They also utilize T cells to attack myeloma cells. We now have three approved bispecific antibodies. Two of them are targeting BCMA, the same exact target that we have in CAR-T cells, and one of them is now targeting a new target called GPRC5D, which is also highly expressed on myeloma cells.  

So, having all these bispecific antibodies available is excellent because patients can have access to them a lot faster and now we’re trying to answer the question of sequencing. Can you give bispecific antibodies after CAR-T cells for example? Can you give one bispecific antibody after another, especially if there’s a different target that we now have available?  

As a whole, though, bispecific antibodies tend to have lower response rates than CAR-T cells, particularly cilta-cel (Carvykti), which is cilta-cel that has a very high response rate of close to 100 percent.  

Most bispecific antibodies have response rates somewhere around 70 or so percent, so about two-thirds of patients respond to these therapies, again, in that fifth line or four or more lines of therapy. So, in that space, that’s the response rate. And across the board, generally speaking, patients benefit from these bispecific antibodies approximately a year on average. Some of the studies have shown longer benefit, and it also depends somewhat on response to therapy.  

Patients that have a really deep response can go even way longer than that. So, it is quite mixed in terms of how somebody may do on these bispecific antibodies, but those are the numbers.  

Katherine:

Well, it sounds like bispecific antibodies have really transformed myeloma treatment options.  

Dr. Nadeem:

Absolutely, and what goes hand in hand in this.  

I mentioned the logistics of CAR T, but then there’s also the supply and availability of CAR-T cells. Since the approval, the demand for CAR-T cells has been very high because of all these excellent results, but the supply really hasn’t been there. So, even at a center as busy as ours, we can only treat a handful of patients with CAR T-cell therapies compared to bispecific antibodies, where that is essentially an injection similar to many other approved myeloma agents that you can just readily treat patients with. So, CAR-T cells, while I think, again, have higher efficacy, with that comes slightly higher toxicity as well. It’s a very different kind of treatment program.  

And then, patients get a treatment-free interval, which you don’t see yet with bispecific antibodies. On the other hand, bispecific antibodies are readily available, slightly lower response rates, slightly lower toxicity when it comes to at least the traditional T-cell directing toxicities. And then you have, again, the readily available nature of it, which I think is hugely beneficial for patients.  

Katherine:

You talked about some specifics regarding bispecific antibodies, but are there updates in bispecific antibody research that you’d like to share? 

Dr. Nadeem:

Yeah, so, again, kind of following the theme of what we just said about CAR-T cells, can you bring these antibody therapies earlier? And there’s ongoing trials now looking at it in newly diagnosed multiple myeloma and early relapses, and then we presented our data at ASH this previous year looking at it in high-risk smoldering myeloma. We treated patients with teclistimab (Tecvayli), which is a BCMA bispecific antibody that is approved for relapse refractory patients. And what we demonstrated in that study is that people that got teclistimab had a 100 percent response rate with an MRD-negative rate. So, kind of as deep of a response as we can measure, also at 100 percent.  

So, this is something that we had not seen before. When their immune systems are a lot healthier, they may benefit more. So, hopefully we’ll see confirmation of these results in other trials.  

Particularly in the newly diagnosed space because we do think that these antibody therapies have such huge potential to treat patients, and then hopefully we’ll have durable responses. So, I do think that some of this paradigm may shift over the next few years, and then there’s also combinations that are currently being studied: combinations with traditional myeloma therapies, such as monoclonal antibodies, other immunomodulatory agents, or proteasome inhibitors. All these combination trials are now ongoing to see can you improve upon some of those numbers that I highlighted before with single-agent bispecific antibody therapy. 

Katherine:

Can you share the pros and cons of bispecifics and how it compares to CAR T?” 

Dr. Nadeem:

Yeah. I think we mentioned earlier that as a whole, they’re very similar. They’re both T-cell re-directing therapies, in many circumstances, with the same exact target of the myeloma cell, but because this isn’t a cell infusion – this is a cell injection – that you receive that redirects your T cells to the myeloma cells, you tend to see a little bit of a lower toxicity signal when it comes to the cytokine release syndrome incidents and severity. You see lower neurological toxicity, usually, than you do with CAR  T-cell products as a whole.  

With that comes slightly lower efficacy than you see with at least some of our CAR-T products, but if you respond to therapy, then the durability of response can be as good as you can achieve with CAR-T cells. One thing to note about the bispecifics, though, is that it is continuous therapy, so you are getting it on some regular schedule. Right now the approval is for it to be given weekly and then go to every two weeks after six months of therapy if you’re basically in a good response.   

A lot of that is to try to mitigate the risk of infection. So, that is one of the biggest things that we have seen with bispecifics more so than CAR-T cells. Because it is continuous administration of these therapies, that really suppresses your immune system significantly, and infection rates are quite high. So, we typically give other ways to try to mitigate that using immunoglobulin infusions to try to boost up your immune system. Typically, we do that once a month for patients, making sure you’re on the right prophylactic medications and then really adjusting the therapy and the schedule to you depending on your tolerability.  

So, as we said before, it’s an excellent option. I think bispecific antibodies are going to be the mainstay of myeloma therapy going forward because CAR-T cells, again, we can’t really treat everybody with CAR-T cells just simply because of the dynamics of how the process is. So, having the bispecific antibodies available for patients is excellent.   

Can Race or Ethnicity Impact CAR T-Cell Therapy Response?

Can Race or Ethnicity Impact CAR T-Cell Therapy Response? from Patient Empowerment Network on Vimeo.

Can CAR T-cell therapy response be impacted by patient race or ethnicity? Expert Dr. Sikander Ailawadhi from Mayo Clinic discusses some impacts to CAR T-cell therapy response for African Americans and some clinical methods to help reduce impacts to patients.

[ACT]IVATION TIP

“…there is a lot of work happening, research happening around how to predict and prevent side effects from CAR T so that the patients are much more informed, aware, can make an informed decision, and as clinicians, we can do whatever is within our control and is at our disposal to help prevent those side effects and make CAR T an even safer and more beneficial treatment for patients.”

Download Guide | Descargar Guía

See More from [ACT]IVATED CAR T

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How Are Rural CAR T-Cell Therapy Barriers Being Addressed?

How Are Rural CAR T-Cell Therapy Barriers Being Addressed?

Transcript:

Lisa Hatfield:

Dr. Ailawadhi, is there data around ethnicity and response to CAR T-cell therapy and whether genetic factors may affect treatment outcomes? And can the side effects of CAR T-cell therapy be predicted or prevented?

Dr. Sikander Ailawadhi:

So Lisa, a very important question of whether there are racial ethnic factors that can affect CAR T-cell therapy benefit or side effects, and what are we doing to prevent some of these side effects? We know side effects can happen, what can we do to actually prevent them? So I’ll take this question in two different subgroups. The first one of talking about racial ethnic groups or differences. So we know patients who are African Americans. This is one study reported that African Americans are more likely to have side effects from CAR T-cell therapy.

So while it’s not a specific “genetic factor,” but race ethnicity can sometimes be associated with more side effects, and that is just because these are very inflammatory delivered or inflammatory mediated side effects like CRS. It’s also important to know that there are certain other factors, disease or treatment-related factors, that can help predict potentially more side effects with CAR T. For example, patients who are very heavily pre-treated, patients who have a very high disease burden, patients who did not respond to bridging therapy that was given to them prior to the CAR T.

These are all factors where we know that side effects are going to be more, and the success of the treatment might be lesser. What we are trying to do to mitigate some of these side effects, there are now studies which are giving either some low doses of steroids as a prophylaxis before, right around the time of CAR T, so that side effects may not happen. Studies that are giving a low dose or even standard dose of what’s called tocilizumab (Actemra), toci, or tocilizumab.

This toci drug is an antidote for CRS or cytokine release syndrome. The thought is, well, why wait for the toci to be given after the side effect happens? Why not give it beforehand and prevent the CRS? Historically, there was a concern that steroids or toci given early on could affect the CAR T-cell viability or activity, but that’s not the case. For example, in lymphomas, there are clinical trials that have shown very clearly given prophylactic or preventative steroids could help. Using steroids or toci in a preventative manner is helping mitigate some of the side effects. 

Well, by preventing the side effects, we are being able to give the treatment in a way that the patients may have lesser side effects and can get it done closer to home or at home sometimes, and their time to stay in the hospital is lesser. You can imagine that some of these barriers are being further mitigated.

My activation tip for this question is that there is a lot of work happening, research happening around how to predict and prevent side effects from CAR T so that the patients are much more informed, aware, can make an informed decision, and as clinicians, we can do whatever is within our control and is at our disposal to help prevent those side effects and make CAR T an even safer and more beneficial treatment for patients.


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How Do Race and Ethnicity Impact CAR T Side Effects?

How Do Race and Ethnicity Impact CAR T Side Effects? from Patient Empowerment Network on Vimeo.

How are CAR T side effects impacted by race and ethnicity? Expert Dr. Sikander Ailawadhi from Mayo Clinic shares some research study results about CAR T response rates and disease progression in African American and Hispanic patients and solutions for clinicians.

[ACT]IVATION TIP

“…there are some differences by race, ethnicity, specifically for the side-effect profile, patients should be aware of it, and clinicians who are the CAR T specialists should be aware of it so that they can manage the side effects well in their patients.”

Download Guide | Descargar Guía

See More from [ACT]IVATED CAR T

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How Can Equitable CAR T-Cell Therapy Access Be Increased?

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How Can Information Disparities on Emerging Therapies Be Addressed?

Can Race or Ethnicity Impact CAR T-Cell Therapy Response?

Can Race or Ethnicity Impact CAR T-Cell Therapy Response?

Transcript:

Lisa Hatfield:

Dr. Ailawadhi, real-world data from one of the available CAR-T-cell therapies, ide-cel (Abecma), has shown some differences in the side effect profile and benefit by patient race and ethnicity. What is your take on this, and how do you utilize this in your clinical practice? And also, what do you think researchers should do next to learn more about how CAR T therapies affect different people?

Dr. Sikander Ailawadhi:

This is an extremely important question, looking at what is the data currently on the risks and benefits of CAR T-cell therapy in patients from different racial ethnic groups, and then how are we using that in the clinic today and where should the field go about research in this area. So, Lisa, you’ve correctly pointed out that this study that was published recently is based on some real world data from one of the CAR T cells available, ide-cel.

Now, I shouldn’t say that this is specifically to ide-cel, but basically, ide-cel has been around a little bit longer than cilta-cel (Carvykti), and so the real-world data on ide-cel was to the point that this racial ethnic analysis could be done, and it was reported. That said, we don’t know how cilta-cel would be. That data just does not exist. So, I’m not saying that this is applicable to cilta-cel or not, because at least this study was specifically for ide-cel because that data was mature enough to be reported. That was just a qualifier of this particular question.

Now, what that study showed was that some of the side effects, including CRS, the cytokine release syndrome, and certain markers that can be an accompaniment of CRS, like the ferritin or what’s called CRP, C-reactive protein, which are inflammatory markers. So, inflammatory markers were higher in African Americans, and the CRS was also higher in African Americans from that real-world data.

The other thing that it showed was that the response rates were lower in Hispanics, but the progression-free survival, meaning time it took for the disease to progress and require more treatment, was lower in African Americans or overall survival was same across the racial ethnic groups. So, side effects a little bit more in African Americans, and the immediate response, a little bit less in Hispanics, but overall outcome, similar across races. Now, this is important for us to know because African Americans tend to have certain inflammatory disorders more frequently, like even asthma is seen more frequently in African Americans.

So, CRS, which is an immune system mediated inflammatory response, I can imagine that some of it might be higher in African Americans. So, in our clinics, what we are doing is when we are monitoring the patients, every patient is getting monitored the same way, but when it’s an African American patient, we are putting a little bit more focus on those inflammatory markers that can sometimes start showing up even before the CRS happens. I don’t think the response rate portion of Hispanics that we’re really taking into account much because the overall outcome or the long-term outcome was not really different between races and ethnicities.

Of course, there needs to be much more research, so I think we need longer-term follow-up data, we need larger number of patient data, and what I alluded to in the very beginning, we do need data on cilta-cel also, which has not yet been presented, but we are hoping that it will come out very soon. So, my activation tip for this question is, that there are some differences by race, ethnicity, specifically for the side-effect profile, patients should be aware of it, and clinicians who are the CAR T specialists should be aware of it so that they can manage the side effects well in their patients.


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