ELEVATE | From Research to Recovery: CAR T-Cell Therapy for Myeloma Patients

Transcript

Laura Beth Ezzell:

Hello, and welcome. I’m Laura Beth Ezzell, your host. Today’s program is part of the Patient Empowerment Network’s Elevate series, which aims to help patients and care partners feel confident and well-informed when making care decisions with their healthcare team. Whether you’re newly exploring CAR T-cell therapy or supporting a loved one through treatment, today’s discussion will provide you with key information to empower you. 

Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice.  

Please refer to your healthcare team about what might be best for you. Okay, let’s meet today’s guest. Joining me is Dr. Ciara Freeman. Dr. Freeman, can you please introduce yourself?  

Dr. Ciara Freeman:

Yes, happy to, and thank you for the invitation to chat with you today. My name is Dr. Ciara Freeman. I am a cellular therapy doctor working in the Moffitt Cancer Center here in Tampa, Florida. My area of interest is in using complex cellular therapy like CAR T-cell therapy to treat patients with hematological cancers like myeloma, especially myeloma.  

It is the area of interest that I focus my efforts on, both from clinical trial, at execution, and also from working on the bench in the lab, as well. So, we’re doing a lot of work here at Moffitt to try and really advance the science, and really cement the foundation of CAR T-cell therapy for patients with myeloma.  

Laura Beth Ezzell:

Excellent. Well, we appreciate you taking time out of your day to join us. And before we get into the discussion, I’d like to just start by discussing your role as a researcher.  

You play a pivotal role in moving myeloma care forward. So, what inspired your work in this field?  

Dr. Ciara Freeman:

It’s a great question. It’s something that I’ve been passionate about for quite some time. Myeloma is a disease where innovation really changes lives. When I first started out learning about hematology and blood cancers as a student, myeloma patients had a very dismal prognosis. 

And there has not been more innovation, I would say, in any cancer field that has been more impressive over the last number of years than in the setting of multiple myeloma. We’ve seen more drug approvals. We’ve seen greater advancements. Early in my training, I’d seen patients who’d exhausted every available option, but the biology sort of suggested to us that the immune system still had this tremendous untapped potential, and we’re really just seeing that now.  

We’ve seen incredible developments in CAR T-cell therapy, where basically, we take a patient’s own immune cells out, engineer them, and then put them back in the patient’s body to recognize, and seek and destroy, and kill those cancers.  

And it’s no longer experimental. It’s now becoming a core pillar of what we do. And so, it’s been something I’ve committed to ever since, helping translate that promise into durable, real-world benefit for patients.  

Laura Beth Ezzell:

Yeah, so interesting, and thank you for setting that up for us. We’re on the heels of the annual meeting of the American Society of Hematology, where blood cancer researchers from around the world come together to share their research. So, can you start by sharing maybe some of the highlights from that meeting, particularly relating to CAR T-cell therapy?  

Dr. Ciara Freeman:

Absolutely. Again, I said, CAR T-cell therapy is no longer experimental. It’s a real, core pillar of what we’re doing now. We’ve seen ongoing deep responses from some of the approved CAR T cells that have already come through and have FDA approvals, even in heavily pretreated patients.  

We’ve seen more data come through in earlier line use, suggesting that patients who get treated earlier probably have better durability when it’s used earlier in the disease course. We’re seeing great momentum around dual targeting, so, targeting more than one marker on the surface of the cells. We’ve seen next-generation constructs trying to prevent relapse.  

And, of course, we’ve got a huge input here from our own real-world data. We’ve seen an incredible amount of data coming out from the consortium that we are a part of at Moffitt, led by Dr. Hansen, looking at real world outcomes; toxicity, mitigation, and patient selection.  

So, the field is really moving from “Can this work?” to “How do we make it better, safer, more durable, and really get it out to more and more patients?” 

Laura Beth Ezzell:

Yeah, such incredible and just promising news, and I can just tell the excitement in your voice while you’re talking. So, I love that. And just before we go on, Dr. Freeman, can you provide maybe a refresher for our audience? I know you touched on it just a second ago with taking cells out of the immune system. 

So, how does CAR T-cell therapy actually work?  

Dr. Ciara Freeman:

So, how I usually describe it to my patients is their own immune system has ignored the cancer that’s living there. It’s for some reason. I say that the cancer put on some glasses with the little funny mustache, and it’s hiding from them. And so, what we’re doing is we’re sort of refocusing the immune system back onto the cancer, to kill and destroy.  

So, in the setting of CAR T-cell therapy, what we’re doing is we’re taking out what I call them the basic recruits. So, the patients own T cells that reside in their body, and we send them off to bootcamp; and we send them off to bootcamp to turn into Navy SEALs. And how that happens is they’re basically genetically engineered to express on their surface something that recognizes the cancer cell when it meets it.  

And a signaling piece that goes into the cell and says, “When you meet this thing, you get all jazzed up, and you attack like crazy.” And so, that’s the sort of basic loop. 

We send the basic recruits off; they get manufactured into a little army of cancer-killing machines; and then, we get the patient back; we make sure that they’re fit and ready and all primed to receive these little armies; and we put the cells back in the patient’s body, to seek and destroy. And that is somewhat complicated, and sort of a process that isn’t available on everyone’s doorstep.  

So, it’s really something that’s primarily been focused on centers like Moffitt, where we have all the capabilities to really manage patients well. But we’re working hard to sort of make that process as efficient, and streamlined, and effective as we possibly can.  

And we know that once you put that little army back in, it has outperformed standardized approaches with combination chemotherapy regimens in trials, head to head, over and over again, we saw updated data; overall survival benefits for patients who got CAR T in earlier lines of therapy compared to standard of care. So, it’s an exciting space. It’s definitely something that we want to build upon and grow for our patients. 

Laura Beth Ezzell:

Okay. I love that explanation. I can totally picture the Navy SEALs there. So, I think that’s a great way to explain that to your patients. And can you share, maybe, how CAR T has changed over the last few years?  

Dr. Ciara Freeman:

It’s definitely evolving. Certainly, from work we’ve done, when we first had CAR Ts in our hands, the first approval came through in 2021 for multiple myeloma patients. We were treating patients who’d really exhausted every single tool we had in our toolbox. Some of the patients we had coming forward for CAR T-cell therapy had been on therapy almost continuously for over a decade.  

Some of them had had a median of like six prior lines of therapy. Some of them had 12, 13, 14 prior lines of therapy. So, the idea that they would come and have this treatment, and be off treatment for the first time in a decade, was sort of life-changing for them. Regardless, I think what’s important is to really manage the patients well.  

So, I think what has really come through for us is our ability to identify patients in an earlier treatment line, ideally sequence things in such a way that we’re using CAR T earlier than we were previously, because now we can. We’ve seen FDA approvals come through in earlier treatment lines. Similarly, we’ve got trials open in earlier treatment lines, where we’re exploring this, so that we’re basically taking the patient’s own immune cells out at a point where they’re not so beaten up.  

So, you don’t want to send off tired, exhausted recruits who’ve been in the war for years and years and years fighting a battle, to then become Navy SEALs. What you want is those youthful, fresh, ready-to-go recruits to go off and become SEALs in bootcamp. So, I think that that’s been something we’ve learned a lot.  

The other thing we’ve learned is how to manage the enemy. So, what’s come out, has been really important, is having a patient who’s been what’s called bridged. And what that means is their disease is well controlled, in between that period where we take the SEALs out, or we take the recruits out and we send them off, and we get them back.  

And in that window between cells gone and cells back, that we manage the disease that the patient has very well. So, that’s called bridging therapy, the bridge to CAR T. And I think what we’ve learned is that, you know, patients who were a better bridge, who got low disease burden on the way in, tend to have better outcomes. They’ve got less side effects. They respond better. They’ve got greater depth and durability response.  

And again, how I explain that to patients is, if you’ve got less enemies to overcome, those SEALs have got an easy mission. They just go in, seek and destroy, very little fallout. You’re not setting the whole town on fire. So, that’s sort of how I explain it to them, is it’s important to do those things. And then, we’re also managing the aftercare much better.  

So, we’re watching out for infectious complications. We’re watching out for risk of other things. So, I think we’re overall doing a lot better in terms of how we’re managing patients.  

Laura Beth Ezzell:

Yeah, and maybe just to add onto that, maybe a little more, what do you think researchers have learned from treating and monitoring like thousands of patients after this point, after they’ve received this therapy?  

Dr. Ciara Freeman:

I think there are a lot of things that have come out; as I said, things that are important, using them earlier, using them first, if we can. So, there’s other agents that are coming onstream, such as bispecific antibodies, which for people who are not familiar, they’re an antibody that has one end that attaches to the cancer cell, and one end that attaches to the immune cell, and it brings them together.  

And what we know is that if patients are exposed to continuous bispecifics, that is basically getting their recruits to do a lot of work, week after week after week. And then, you try and make CAR-T cells with the same target after that; they tend not to respond as well, because to some extent, the recruits are tired, and they’re not ready to become Navy SEALs. They’re exhausted at bootcamp.  

The other thing is that it seems to be that after continuous use of a bispecific, the target itself can change, and that happens more frequently in patients who get continuous bispecifics than patients who get CAR T.  

And so, our sort of mantra here at Moffitt is, if the patient is eligible for CAR T, we should try and do that first; and a lot of that came out from real-world data, that the sequencing matters. And so, if we can, we offer a patient CAR T-cell therapy first, either FDA-approved or on clinical trial, and we hold the bispecifics if we can, for later use.  

And that, in our view, at least as of right now, may well offer the patient a longer trajectory, such that if and when the CAR T eventually stops working, we have the bispecifics that are still ready for us to use, and there’s a lot of evidence to suggest that patients will still respond well and get more durability if we do it in that way than the other way around.  

Laura Beth Ezzell:

Yeah, that’s interesting just to learn about the whole process, and what you have learned to this point. And continuing our discussion about just progress in the field here, let’s talk about next-generation CAR T. So, what’s coming down the pipeline, and how are these different from currently approved CAR T-cell therapy? 

Dr. Ciara Freeman:

So, we’re seeing novel targets. So, certainly we’re seeing CARs being developed that are going after a different marker. So, for example, we presented data from a trial in progress of a GPRC5D targeting CAR. That’s a very painful, long-winded name for a target, but essentially it’s a different target to the one that is currently being exploited with everything else that’s been approved with the exception of a bispecific.  

So, that trial is specifically enrolling patients who have failed all of the tools in our toolbox, including a BCMA-directed therapy. So, we’re definitely seeing novel targets under evaluation, and that trial is a pivotal trial, and we’re recruiting at Moffitt right now. We’re seeing dual-targeting CARs. So, pairing BCMA with another target, to try and reduce this theory of what’s called antigen escape.  

So, basically where the myeloma cells can evade by hiding one target, and having another one there, means that the CARs have two opportunities to basically attach and kill. So, doubling your money, if you will, like betting on two horses rather than one. We’re also seeing armored CARs come through. So, they’re designed to basically resist the suppressive environment around them.  

So, you can imagine sending your recruits in with more weapons, to sort of get things out of their way. We’re definitely we’re seeing more data on how we can improve T-cell fitness and persistence. So, one of those things is obviously to get the recruits out earlier, to use the T cells earlier, but there are also manufacturing techniques that have been explored, how we can basically manipulate that in a manufacturing point of view. And then, the other thing was very exciting at ASH, seeing off-the-shelf therapies. So, one of the late-breaking that came out at the ASH meeting was an in-vivo CAR. 

So, a CAR where instead of sending the recruits off to bootcamp, you host the bootcamp in the patient’s body. So, that was a very exciting, obviously very small data set very early, but making the whole process much more streamlined and efficient, and also eliminating the need for the chemotherapy that we give before we put the SEALs in. All of that would be if we can show that this is a successful approach. That will totally change our current delivery paradigm. It will be very exciting for patients.  

Laura Beth Ezzell:

Yeah, absolutely. That sounds very promising there. And Dr. Freeman, can you talk about the advances in manufacturing T cells?  

Dr. Ciara Freeman:

Yeah. So, that’s obviously another area where we can improve things. So, how fast the cells get turned around has not only got an impact on the patient experience, because obviously if a patient has to wait a very long time, there’s a chance that we could lose disease control while we’re waiting for the cells to get made. So, those SEALs have got to get made quickly. 

But we also don’t want them to get too flogged at bootcamp, so that by the time we put them back in to seek and destroy, that they’re exhausted. And so, what we’re seeing is manufacturing that is faster, more consistent, and trying to sort of optimize the T-cell quality to preserve the younger, more kind of what’s called naïve cells, and also reduce variability. So, having a more consistent product delivered for patients. These are all key steps towards broader access and better outcomes.  

Laura Beth Ezzell:

Excellent. Okay. Now that we’ve covered all the recent innovations there – and you did a great job explaining all of that, and I appreciate that – let’s understand a bit more about the CAR T journey for patients. What can the patients expect prior to the CAR T-cell therapy process?  

Dr. Ciara Freeman:

So, the first thing is a patient will come to a physician like me, and we’ll have a discussion, and we’ll review their history to date, and everything that has happened; the kinds of therapies that their disease has seen, or not seen, if it were. 

And then evaluating what makes the most sense to that patient, and whether that’s a clinical trial, or whether that’s a CAR T that’s commercially approved by the FDA, and then selecting the right fit for that patient. There’s usually a period of evaluation where we make sure that the patient is in good condition, that they could handle the physiological challenge of the aftermath of after we put those Navy SEALs in; although we’ve shown that if you optimize the patients well, even patients who are older do very well with CAR T-cell therapy. 

After that period of evaluation, we’ll then obviously take the cells out, and send them off, if they’re getting manufactured outside the patient’s body. And then, as I said, this bridging therapy, this treatment to keep their disease in check, between when we send the cells off and when we get the cells back. Education is critical. So, patients and care providers need to understand the timelines. And obviously, we spend a lot of time explaining the potential side effects, and the importance of staying engaged with their care team.  

We have a fully outpatient program here at Moffitt. So, we don’t routinely admit everyone, which is great for patients. They tend to eat better, sleep better, move around more, and they do extremely well. And then, in terms of providing advice for patients and their care partners, we prepare them really extensively, both medical and practical.  

We make sure they have a reliable care partner. We plan things very carefully. We make sure they ask their questions early. And we also have a lot of focused initiatives looking at nutrition, activity, and prevention of an infection, because obviously, patients who are really informed tend to do better, not just physically, but also mentally and emotionally.  

Laura Beth Ezzell:

Yeah, absolutely, and glad that you’ve kind of gone into this preparation involved to get ready, because I’m curious, what advice do you have or do you share with patients and caregivers on how to best prepare during the time before therapy? 

Dr. Ciara Freeman:

So, we actually had a number of investigational trials that we had here at Moffitt, in preparing patients for therapy. So, we had what’s called a prehabilitation trial. That was where we basically picked our only our older patients. You had to be over the age of 65 to be enrolled, and we basically gave them a prescriptive strength training and exercise training regimen to do while they were preparing for CAR T.  

And what we found was that patients not only were engaged and very motivated, and felt really empowered by this approach, but they also seemed to have a reduced length of stay. So, you’re in the hospital for a shorter period of time compared to sort of matched peers, and they had a better overall experience. The feedback that we got from patients was extremely positive, and we had very little in the way of any side effects.  

So, certainly, it’s something that I encourage my patients to do. The answer absolutely is be active, move about, use your muscles, because a lot of the patients have been on multi-agent treatment, high dose steroids for a really long time. And so, they’ve lost a lot of their muscle mass.  

And so, that’s going to sort of mitigate their ability to recover quickly after CAR T. Same thing, we have a study open right now, looking at the effect of dietary intervention prior to CAR T. So, we’re looking at a ketogenic diet, and whether that will improve their basic recruits. We make them fitter by putting them on a diet. And so, that’s a really exciting study that we’re doing right now.  

Again, patients love it. We provide all their meals. So, they don’t have to worry about cooking or anything for the whole time. It’s all done work with our fantastic nutrition team, and our research kitchen. And so, that’s obviously something else that I feel very strongly about, is the importance for patients to eat well, to eat good food that is good for their bodies. And we’ll see whether we can sort of make those T cells fitter with that intervention. It’s going to be exciting to see those data come out.  

Laura Beth Ezzell: 

Yeah, great to just learn about what you do with patients there in the process. And just moving on to the CAR T process, let’s help our viewers better understand what to expect when they’re actually undergoing therapy. First of all, how long does the process take?  

Dr. Ciara Freeman:

So, once we get the product back, usually we’ll see them fairly quickly. We tend to plan anticipating when we’ll get the product back. So, we’ll usually get a heads up from whoever’s making the cells. This is when we’re most likely going to get the cells back, and we’ll plan for the patient to come accordingly.  

As I said, we have a fully outpatient program. So, we don’t admit patients unless there’s a mandate as part of their clinical trial that we have to admit them. And so, they’ll come. They’ll see their primary team, make sure everything’s going okay, and that they’ve had a good response to their bridging therapy, and that they’re well.  

And then, basically, we start seeing them as an outpatient. So, basically, we see them every day. So, they’ll be seen the day before they start. And then, they have their three days of chemotherapy, which prepares them for the CAR T to go in.  

That three days of chemotherapy is fairly standard across all the products and trials, where the cells are the patient’s own cells that get sent off and are put back in the patient’s body. And then, the cell infusion happens two days later. The infusion itself is brief, and sort of some patients will consider it to be somewhat of an anti-climax. It’s a very small amount of product that goes in, for something that seems like such a big deal.  

Oftentimes, nothing happens for an initial period of time. So, the products vary in terms of when they will cause what’s called cytokine release. So, that’s where the cells meet the tumor, and they get all jazzed up, and they release these chemicals called cytokines; and that can cause a flu-like syndrome in the patient.   

That’s called cytokine release syndrome. When that happens, the first fever, we will admit the patient for observation. And we bring them in, make sure that they’re doing okay, make sure that there isn’t an infection that we’re missing, and keep a close eye on them and monitor them very closely. 

The FDA recently changed their guidance about how long a time the patient has to remain near a major center like Moffitt for monitoring. And so, we’re evaluating how long it is before patients can reasonably be allowed to go home. So, there was a period of time where patients were told they couldn’t drive for eight weeks. And then, we did a lot of work with the consortium, showing that patients really didn’t have any neurological issues that persisted beyond the first month.  

And so, that mandate was lifted, that patients could drive sooner than that. So, usually sometime between three and four weeks after the cells go in, the patients are able to go home and basically sort of recuperate from the process.  

We’ll monitor them quite closely. And obviously, if anything happens at home, they’ll call us, let us know, and then we’ll decide whether we bring them back for an evaluation if they’ve got an infection brewing, or there’s something else that we’re worried about. And then, we see them periodically for disease assessment, response assessments, and vaccines. 

So, we revaccinate our patients after CAR T. So, that’s the general overview, but what patients really love is, in the overwhelming majority, after the CAR T goes in, they’re on no treatment directed towards myeloma for the first time in a really long time, and they really love that. They love being off therapy.  

Laura Beth Ezzell:

Okay. So, there’s nothing extra that they’re doing in between this time.  

Dr. Ciara Freeman:

No, it’s more just about keeping an eye on things. So, some patients will have sometimes a low immunity, and so, we’ll support them with pooled antibody therapy.  

So, that’s something that we do often do once a month for the first period, just to keep them well, and sort of reduce their risk of especially chest or sinus infections while the immune system is recalibrating. Some patients have some minor fatigue or other issues, but most of those are temporary; but close monitoring allows for us to have early intervention, which is key.   

Laura Beth Ezzell:

And, Dr. Freeman, can treatment response improve over time, or is it immediate?  

Dr. Ciara Freeman:

So, treatment responses, certainly in terms of the way that we measure them, especially in myeloma, can absolutely deepen over time. So, what we see, for example, in patients who have what’s called this monoclonal protein, it’s quite a big and heavy molecule.  

And sometimes, what we’ll see – and if we do, for example, lab work early – they’ll still have this measurable protein that has been made by their cancer cells, even though all the cancer cells the next time we look in the marrow are completely obliterated and gone, and they’ve got no evidence of any disease anywhere. And what happens is sometimes that M protein takes a long time to be broken down by the body. So, when we map it out over time, it’s just gradually decreasing, kind of decaying over time, if you will. And so, that’s where we’ll see those deepening responses over time.  

Laura Beth Ezzell:

Yeah. And related to follow-up care with your healthcare team, how often do patients undergo follow-up scans and testing?  

Dr. Ciara Freeman:

So, patients will have regular blood tests in the early days, especially when we’re trying to monitor how they’ve recovered in terms of their counts, and making sure that they don’t need any support for transfusions, et cetera. And then, we’ve got quite a standardized approach to when we’ll do bone marrows and imaging and reassessments, and we try to not overdo those. It’s important for us to make sure that we’ve got an early indication of how patients are doing, but also these are procedures that patients don’t want to have, if they don’t need them. 

So, we’ve got quite a strict protocol, where we’ll do them at the early time point. The earliest time point that we’ll often do those kinds of testing, marrow and PET scan, is at 90 days. So, about three months after the cells. And then, we often won’t do them again until a year out, outside of clinical trials. So, in between time, they’ll have regular lab work done, keeping an eye on their counts and keeping an eye on their myeloma labs.  

Sometimes we’ll do a little bit more imaging, if patients have the kind of myeloma where it mostly forms lumps in the body, rather than is followed by the blood. And so, ongoing assessment is definitely tailored to the patient, and we keep a close eye on them, depending on what makes sense for their body and their disease.  

Laura Beth Ezzell:

And can you explain what MRD negativity means?  

Dr. Ciara Freeman:

Absolutely. So, it’s a certainly a very important topic in patients with multiple myeloma. MRD stands for minimal residual disease. Some people say measurable residual disease. There are a number of ways that you can do it. You can do it with a super fancy flow-based assay, or you can do it with a genetic assay called next-generation sequencing. A common company that’s used by a lot of providers is called Adaptive, and they do something called clonoSEQ.  

How I describe it to patients is they basically get a fingerprint of your original disease, and as long as they can get that original fingerprint, then they can use that fingerprint to look at a high level of sensitivity in every bone marrow that you have sent off after that time point. So, with the next generation sequencing, you do need that index fingerprint. If you don’t get that index fingerprint, you can’t follow it over time.  

Once you get it, you can actually look for evidence of multiple myeloma at a sensitivity of one in a million cells. So, you can take out four or five million cells out of the bone marrow, send them off to this company, and then find whether there’s zero, at a sensitivity of one in a million. 

And that’s the golden number that all patients want to get to, where we looked as hard as we could, and even one in a million we can’t find. It’s certainly one of the strongest predictors of long-term disease control.  It’s certainly part of the bigger picture, but not the whole story.  

So, we need to also make sure that we’re keeping an eye on patients with imaging, as well, because sometimes their marrow is very well cleared out with CAR T-cell therapy, but sometimes we’ll see what’s called extramedullary disease. And that’s where the disease relapses outside of the marrow, and we only see that on imaging. And sometimes, we miss out if we only look at the marrow.  

Laura Beth Ezzell:

All right, so, let’s now consider the long-term recovery here. A close monitoring is still important, obviously, as time passes. So, what are the symptoms that appear in the months after treatment?  

Dr. Ciara Freeman:

So, it can sometimes depend on the product received. So, there are some products that we are a little bit more cautious for, in terms of longer-term late onset relapses or toxicities. So, there are certain products where we’ll tell patients, even though you’re going home, if any of these things happen, we’ll want to make sure that you let us know early, and don’t sort of write it off as not something that’s important to report.  

Some of the things that we watch out for are unusual, uncommon neurological side effects that some patients can report. So, we’ll usually have quite a detailed sit-down with a patient at Day 30, and explain to them, “These are the things I want you to tell me, if they’re occurring. Even if you think it might not be related, I want you to let me know.” 

Any patient with multiple myeloma, regardless of the stage of their disease, is, unfortunately, at increased risk of secondary malignancies. So, that’s other cancers outside of their myeloma. So, any patient I meet, whether it’s newly diagnosed, early relapse, late relapse, I’ll always tell them, “Let’s make sure that we don’t forget about keeping an eye out for those other cancers.”  

And those could be your standard age-and-sex-based screenings like mammograms, and keeping an eye on your prostate, if you’re a man, and colonoscopies, if you need them. These are all things that I also want to make sure is incorporated into every patient’s long-term for survivorship plan.  

Laura Beth Ezzell:

Yeah, and how long will patients need to be on preventative antibiotics or antiviral medications?  

Dr. Ciara Freeman:

So, the antibiotics, we stop early. As soon as the patient’s recovered what’s called a neutrophil count above a certain threshold, we will not continue those antibiotics. There are certain medicines that we do continue. So, the antiviral, continue to the first year after CAR T-cell therapy, and that’s just to make sure they don’t have a shingles reactivation. 

Our patients are always at increased risk, and we’ve taken the same approach that we take from after transplant; and we sort of translated that across to post-CAR T, and we continue that for a full year. And thankfully, we see very few shingles reactivations as a result of that approach. The other thing we watch out for is preventing a sort of very unusual infection called PJP, and we basically keep a very close eye on a certain component of the patient’s immune system.  

And as soon as that’s recovered, we stop the medicine for that; but that’s either a low dose – I guess it is a low-dose antibiotic, or a preventative medicine for that, to make sure that those patients don’t end up getting that nasty lung infection, if it occurs. Because the antibiotic is so narrow in its spectrum. And so, devoid of side effects, we tend to continue that, until they’ve recovered that T-cell component that helps protect them from.  

Laura Beth Ezzell:

Excellent. And this is a question that definitely keeps coming up through my mind. When is it safe to let your guard down a little bit?  

Dr. Ciara Freeman:

So, I think that’s a question that we’ve never been fortunate enough to ask in the myeloma field until very recently. So, many of the patients who are watching this today may be familiar with the data that came out not that long ago, from the long-term follow-up of one of the most potent CAR T-cell therapies, where patients who had been followed out beyond five years, there was a third of patients who were treated in that study who were still in remission after five years.  

And that is on no therapy, on no ongoing treatment, no maintenance, no sneaky chemo put in here and there; and that was a very sort of provoking piece of data to come out for the myeloma community, thinking to ourselves, is it possible?  

Is it possible it might not come back? I think we’re still nervous to say the C word out loud for patients with myeloma, and that’s something that we’re getting more and more excited about. What does that mean? What would functional cure look like? 

How long would they have to be disease-free, in remission of therapy, for us to say you are free of myeloma forever? And from the point of view of me as a patient, as a provider who looks after patients with CAR T-cell therapy, as long as they are well, if they’ve had CAR T-cell therapy, I’ll never discharge them. I will see them less frequently, but I will not let them out of my practice. I’ll keep an eye on them.  

And that’s just good survivorship care. I think it’s mandatory for us to follow these patients, because it’s still an evolving field, and it’s important for us to know what happens, and follow them for as long as they’re alive. And hopefully, as I tell my patients, “I hope that you live long enough to die from something else, and it’s not the thing that you see me for.” 

Laura Beth Ezzell:

Yeah. Yeah, thank you, Dr. Freeman, and your care and concern even through all of this. It comes through so well, and I know it’s part of your patient care, and their healing, as well. And this information has been so helpful to our viewers.  

As we close the program, what key takeaway would you like the audience to remember, and what fuels your hope for what’s ahead?  

Dr. Ciara Freeman:

So, I think the most important thing for any patient with myeloma is to remember that you’re not alone, and although it might not seem as common a cancer as some of the other cancers that are out there, breast; there’s still a huge community. My patients and many patients that come to me are incredibly well informed through initiatives like this one. 

And there are a lot of patient support groups, patient advocacy groups where you can learn more and more. I think the most important thing for patients is to, number one, make sure that they’re connected with a center where there’s the latest and greatest things. They don’t have to get all their therapy there, but it’s good to have a touch point in a big center where they’ve got these trials open and accruing. It gives them access to something that they might not get in the community for some time, until it gets FDA approval.  

Ask bold questions. I think that there’s some great information out there now, especially with the assistance of some of these AI technologies, to sort of decode what your doctor says and help you better understand what’s going on, because it’s not a straightforward disease. Sometimes it’s hard to get your head around the lab tests and what they mean.  

And so, I think that there’s a lot of great initiatives out there to help explain things. And bring those questions to your provider. Patients who go to major centers have improved survival. So, if you at least can connect with a center where they’ve got that expertise, where they’ve got a huge number of myeloma patients, the likelihood is you’ll get access to expertise and treatments that you might not get locally, because you can’t have them everywhere.  

And so, I think that would be my major focus point. Empower yourself with information, and be hopeful, because the survival has been improving every single year that I’ve been in practice. And I don’t even know how to tell the patient now how long that they’ll be alive. 

My goal is to make sure that every patient lives just as long as somebody who is the same age and sex as them, and doesn’t have myeloma. So, I think, yes, we can’t call it cured yet, but we’re definitely making great shapes to getting closer and closer with every day that goes by.  

Laura Beth Ezzell:

Well, that’s a very hopeful note to leave our audience with today, Dr. Freeman. Thanks for taking time to join us.  

Dr. Ciara Freeman:

It was a great pleasure. Thanks for having me.  

Laura Beth Ezzell:

To learn more about CAR T-cell therapy, and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Laura Beth Ezzell. Thanks for joining us.