®. I am Loretta Nastoupil from the University of Texas MD Anderson Cancer Center, and I’m joined today by one of my patients, Brian, and his wife, Denise. Brian is going to share his story of diffuse large B-cell lymphoma, including diagnosis up through treatment, alongside his wife, Denise. Welcome, Brian and Denise.

 I’m going to start with giving a brief overview of diffuse large B-cell lymphoma. Brian, you’ve been diagnosed with diffuse large B-cell lymphoma. This is our most common lymphoma subtype. When I meet patients in the clinic, I make a point to let them know there are 60 different types of lymphoma. Though we use the term non-Hodgkin lymphoma frequently, it’s probably a disadvantage for patients and providers because that encompasses everything that’s not Hodgkin lymphoma.

Once again, diffuse large B-cell lymphoma is our most common subtype. Oftentimes we think of it as being curable with standard treatment, but you’ll hear Brian’s story; that’s not true for all patients. The most important thing is recognizing that there may be many treatment options available for patients, and there’s generally not a one-size-fits-all.

But the point of today’s video is to walk you through one person’s journey and how they’ve been a part of some of the latest treatment breakthroughs, and what that was like both from an adverse effect standpoint and also from his family’s standpoint, watching him go through this process.

Brian, please walk us through your initial diagnosis.

 It started about five and a half years ago. I had a pain in my side, which I understand that’s not always the case that you actually feel something, but I did have some discomfort in my side. Went to my primary care physician, and he decided to do a sonogram just to be safe.

The sonogram showed some tumors around my liver, and that started the ball rolling. I ended up going to a liver specialist in our hometown, and she did a biopsy. It was a very difficult diagnosis once we got the biopsy. It took weeks if not months to get a return on the biopsy for the diagnosis.

The initial diagnosis, we went back to the liver doctor and she said, “I’m sorry, you have liver cancer.” They continued to do some more research, endoscopy and colonoscopy, and then she came back and said, “Well, good news, it’s not liver cancer, but it’s colon cancer.”

We did some more testing and more biopsies, a lymph node biopsy, and then they came back with the diagnosis of lymphoma. It was an interesting journey to get to that point. It took us a while, but that’s what they finally diagnosed me with.

 What were your thoughts when they told you that you had lymphoma?

 My dad had actually died of pancreatic cancer and that thought, being in a major organ, concerned us. With quick research, we saw there was a lot of hope with lymphoma treatments. We were actually almost relieved after getting other diagnoses.

 Denise, what was your experience through this process?

 Just hearing the word “cancer” was devastating to me, especially because he’d always been super healthy, not sick at all. We almost joked that he was super healthy except for the cancer, which was definitely a shock.

I think the hard part, while they were trying to determine the diagnosis and the actual lymphoma that he had and the treatment plan, it was hard waiting because he was deteriorating before my eyes. He was losing a ton of weight all of a sudden, he would have the high fever and the chills every night, and he was just so sick, and I felt helpless because I couldn’t help him. As the wife and mother and female of the family, it was like my nurturing instinct, I wanted to fix things, and that was definitely out of my hands.

 I’ll briefly summarize this presentation. Diffuse large B-cell lymphoma is oftentimes a lymphoma that is associated with symptoms such as weight loss. Occasionally you’ll have pain where the lymph nodes or the masses are growing. If it’s in the abdomen, it’s not uncommon for patients to present with some abdominal discomfort.

As you witnessed, patients can deteriorate very quickly while we’re trying to derive a diagnosis. It’s almost a diagnosis of exclusion, unfortunately, because it’s so uncommon. Having a skilled hematopathologist who eventually gets the sample will finally result in a diagnosis.

 A Diagnosis of Exclusion

Brian, walk us through what your initial treatment was like.

 I did bendamustine and rituximab. I think I did four cycles, and it was uncomfortable. It could have been worse, as far as treatment. I got lot of nausea. I would typically get infusions on a Thursday, and usually by Saturday, I was down for the count and felt pretty bad, like I had the flu. And by Sunday night, Monday, I was ready to go back to work on Monday, and sometimes I would have to take Monday off because I didn’t feel well. But ultimately, it put me in remission, so we were thankful for that.

 Did you pursue any maintenance therapy after the initial treatment?

 We did a two-year maintenance of rituximab after that. I was told I was in remission for two years. And then it was a few months later I had a kidney stone and went to the urologist, and he did a CT [computed tomography] scan and said, “Uh-oh, you’ve got something on your kidney.” We dove deeper into that, and then subsequent biopsies, and realized the cancer had come back.

At that point did you undergo another biopsy? What transpired?

 We did, yes. We did a biopsy. We did another liver biopsy just to be safe. We did a wedge biopsy, so a little bit more than the needle biopsy originally, and then confirmed the diagnosis that it had returned.

 I’m going to clarify one thing about your specific situation. Initially, there were some concerns that this was follicular lymphoma with the initial biopsy, and that’s why you got the bendamustine and rituximab. And then at the relapse, and albeit it was a much shorter remission duration than we would have expected, a biopsy was pursued and that’s when the large cell lymphoma was first confirmed.

At that point you initiated what we call R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], or sometimes patients what refer to as “the red devil” containing chemotherapy. What was that like?

 Before my first infusion, everybody kept talking about the red devil. I was a little worried about that. And it was harsher than the first round. I did lose all my hair, I definitely felt a little sicker after that, but I got through it with my chemotherapy buddy. I couldn’t have done it without her. But I responded very well to that treatment.

And then following that, you underwent stem cell transplant, is that correct?

 I did. That was kind of a tough decision. We had so many questions, and we weren’t sure that was the right path to go. And after a lot of discussion and research with my primary oncologist, we decided that it was worth doing because it had been so successful in putting this lymphoma into remission.

I know that probably at the first sign that you had the lymphoma come back, that must have been a very disappointing situation. Denise, what was your perspective on that, and what do you take away from that?

 It was definitely a shock. It was devastating because once he was in remission the first time, we were thrilled and grateful at the outcome, going through the treatment and the difficulty of that. So, it was a shock for it to return and very disappointing and upsetting, because it seemed like such a short amount of time in which he relapsed and it returned, so it definitely was a difficult time.

Brian, as you mentioned, the R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] is not the easiest therapy to tolerate. What was it like hearing from the transplant team about the intensive chemotherapy that was going to follow with the transplant?

 That’s true. It was rougher than I had anticipated. I did have a lot of nausea. I had trouble, there are so many good medicines out there to control that, and it took a while for us to find the right one. But that was rough. It was nice because I was an inpatient, and so any time I complained or whined about something, the nurses were right there to help me get through that. We got through it. It wasn’t the most fun, but we got through it.

You may be even minimizing what some patients describe. How long did it really take for you to feel like you were close to normal again?

 It was about maybe three weeks to get over it. Would you say more than that?

 I would say more than that. I would say more like four months before he was back to his normal self and having more of his stamina for normal activities without tiring easily.

A Patient’s Initial Treatment for DLBCL

Brian, walk us through, you’re finally feeling close to being back to normal, trying to resume a normal life after undergoing treatment and being a cancer patient for one to two years. What was it like when there was some concern about the lymphoma being back?

 It was a routine follow-up PET [positron emission tomography] scan with my primary care oncologist, and he called and said, “I don’t think it’s a big deal, but there’s a spot on your kidney and near your spine. But don’t worry, we’ll get it figured out.” Again, it was another difficult biopsy. It was in a hard-to-reach place, and so it was probably one of the harder biopsies that I went through.

But they finally got the sample they needed and again, the same situation as before where they had a really difficult time coming up with exactly what type of lymphoma it was. And so again, it was at least a month waiting for the pathology report to come back. I think it had gone several different places, and they finally came up with a diagnosis. So yes, it was very disheartening to get that again. But one day at a time, one step at a time, and we’ll get through it. That was the attitude.

You’ve had more biopsies than the average person, and I think that speaks to the fact that there’s been questions along the way as to what lymphoma we were dealing with, whether it was follicular or large cell, or a component of both. Some patients don’t go through that many diagnoses. But I think your case illustrates how important that information is and how challenging it can be for pathologists to finally give us an answer.

What happened after that? It seems like there was a little bit of a lapse in time.

 We felt like we fell through the cracks, and then COVID-19 [coronavirus disease 2019] hit. So we had to fight, be our own advocate with our local oncologist. It was a crazy time. We finally got firm that we needed to do something. And I had never gotten a second opinion on any of this, and so I had asked my primary oncologist if he would recommend somebody, and he said, “Absolutely. Dr Nastoupil is who you need to see.” That’s how we got down to MD Anderson.

To give people a glimpse of how challenging it can be and how important it is to advocate, your biopsy was late January. You and I didn’t meet until about April or May of this year. And again, recognizing with COVID-19 it’s been a unique situation, but I suspect there are a lot of folks just like you out there sitting around with bad news and trying to figure out what to do with that information, and hurdles and obstacles along the way as a result of a new world.

A DLBCL Relapse During COVID-19

Once you met us, do you remember what we talked about as to what the next steps might be?

 We looked at a trial and thought that it might be the way to go. We met with another doctor there who was heading up that trial and ultimately we decided, because of timing and because I had waited so long to get any kind of treatment, that we go with the CAR-T [chimeric antigen receptor-T cell therapy] as quick as we could.

 For those who are listening along, Brian had a large mass that was starting to replace the function and the anatomy of his kidney. Once we got that scan and realized things had changed dramatically in the months intervening, I didn’t feel that it was safe to explore trial options.

Though I am a clinical trialist and I try to put patients on trials all day long because I think that there are major advantages, sometimes the logistics of getting insurance approval, waiting for those therapies to be lined up, oftentimes adds one to two weeks on to the time course. When you’re someone like Brian where we are already concerned about the loss of function of an organ, sometimes that’s unacceptable.

CAR-T cell therapy was what I recommended. If you recall, and I’ll walk others through it, this is a therapy that’s been FDA [Food and Drug Administration]-approved for adults with large cell lymphoma for just about the last two to three years. It’s relatively new. Essentially what we do is we take your own T cells that are circulating in your body, we collect them through a two- to four-hour apheresis—and we’ll get your opinion on what that was like—and then we send them off to a central manufacturing site so that we can modify these T cells.

Why would we do that? For patients who have lymphoma, just like Denise, you mentioned, oftentimes these are patients who are very healthy, who have not had many medical problems. They’re generally good citizens, meaning they don’t have bad habits that led to their development of cancer. But there is one flaw, and the flaw is that their immune cells, specifically their T cells, are not seeing their cancer cells and they’re not eradicating them like they should.

We’ve spent many years trying to figure out how we might augment that natural process, and probably one of the most direct and effective strategies is to take those T cells out of your body. We’ll use a virus to introduce new genetic material, and so that means those T cells that are yours will now express a receptor, which is outside of the cell. It can engage and bind any other cells that have that target, and that target in your case is CD19, which is a protein that’s only on the surface of mature B cells.

Just like the name of your lymphoma implies, you have a cancer that is a large B-cell problem. It’s fantastic from a targeted therapy standpoint, because we can wipe out every mature B cell in your body, which includes your lymphoma cells, and not really harm you. That’s why it’s been so successful in lymphoma, but yet has struggled to make a splash in other tumor types, because finding a protein that you can target and not harm the host is one of the biggest challenges with CAR-T cell therapy.

But it’s a harrowing time because we collect those cells, we send them off to a manufacturer and it takes about three weeks for that process to happen, and we’re sitting there watching and waiting. In your case we tried bridging therapy, to try and hold you over during that three-week window.

Tell us what the apheresis was like, and then the period following that.

 A year ago I had the stem cell transplant, so I was an experienced apheresis patient. I knew what was coming. With the stem cell I was donating the cells longer than the CAR-T. I knew what was coming. It wasn’t too bad, again, because I knew what was coming. I was able to endure that really well, actually.

Then with the waiting period, we knew what that was like while I did the stem cell last summer and waiting for the stem cells to multiply. It was a similar procedure as far as I was concerned, as far as enduring the apheresis and some other things.

We did the bridge therapy, and that really wasn’t too bad either.

 Denise, you might have a unique perspective on this, because sometimes it’s easy for me to think logistically, step A, we get insurance approval, step B, we undergo apheresis, step C, we wait for the manufacturing. And then once we have confirmation those cells have been modified the way they want and they’re performing the way we want, we bring patients back in, start the chemotherapy to clear out some space, and then we infuse the cells, watch for 30 days for toxicity, and then we bless you and send you on your way. But it was probably much more complicated than that. What was it like for you?

 It was definitely challenging. I think the thing that was different for us is that when he had the stem cell transplant and we were in the hospital three weeks for that, and I did stay in the hospital with him then. They told us to the day what would happen, what his adverse effects would be, how they would treat it, how he would feel, and it was exactly how they said it would be.

And then with CAR-T, because the adverse effects differ to varying degrees, that was quite challenging, just the unknown. Like Brian said, the apheresis part, we were just so thankful to be on a mission for a plan. The waiting part was not a problem, but the side effects threw me for a loop because the neurotoxicity was severe. I might be jumping ahead for what your explanation might be.

But when we were told that the adverse effects could possibly be confusion and some trouble remembering, it was to the max for me. I thought “OK, well, he’ll be a little confused, he might not remember some things, might not know who he is for a little bit.” But because of his degree of the neurotoxicity, it was very scary and very isolating, honestly, because I felt once he had no idea who he was or who I was, it was a different experience and not quite what I was expecting.

But we persevered and he came through great.

CAR-T Cell Therapy for Relapsed/Refractory DLBCL

You bring up some really good points, and one of the most important aspects of how we counsel patients about the potential adverse effects of CAR-T [chimeric antigen receptor-T cell therapy] is the unpredictability of those adverse effects, and also the severity can vary dramatically from one person to the next.

But what I generally tell people is that we’re going to infuse these cells in you after we give you three days of chemotherapy. You’re going to have chemotherapy adverse effects in the background, so you’ll have a lot of fatigue. Blood counts are definitely going to drop, because that’s the point of that chemotherapy. It’s to clear out space so that your T cells that are out circulating are not going to want to remove or compete with those newly modified T cells we infuse in, and so a drop-in blood counts is what we’re hoping for. That puts you at risk for infection.

You can also have nausea, sometimes diarrhea or constipation as a result of that chemotherapy. Then we throw this whole new thing at you, where we give you T cells that have been modified, so that once they engage their target, which is on the surface of your lymphoma cells, they’ll be super-activated. They will release cytokines, they’ll bring in reinforcements, whether it’s other CARs or other normal immune cells that haven’t been modified.

You have this storm of the immune system trying to get rid of lymphoma cells. Oftentimes that will be followed by fever first, fatigue, muscle aches, flu-like symptoms. But the neurotoxicity is harder to predict.

You received axi-cel [axicabtagene ciloleucel], which was the first FDA [Food and Drug Administration]-approved product for adults with large cell lymphoma, and the construct lends itself very well to rapid and successful manufacturing, but also higher rates of acute toxicity, both cytokine release syndrome and neurotoxicity.

I think the neurotoxicity is what really sets it aside. We see as many as two-thirds of patients have some form of neurotoxicity, which we describe just like you recall, Denise. It could be some mild confusion, mild disorientation, slight trouble following simple commands or doing simple math and recall, to the extreme where patients don’t know who they are, they don’t know where they are, or what’s happening to them. They don’t know loved ones that they’ve known for a long time, to even sometimes being completely unresponsive both to verbal stimuli or even sometimes painful stimuli. Then worst-case scenario, we worry about seizure activity or even swelling of the brain that can be fatal.

Fortunately, for the vast majority of patients who have the toxicity, it resolves on its own, sometimes with the use of corticosteroids or tocilizumab, which is an antibody that binds up those cytokines that are driving some of this toxicity. The vast majority of patients will fully recover.

That’s good news for patients. Where we do a disservice is because we know the patient is going to recover and we know that the treatment is worthwhile, we may not counsel patients well enough for this rollercoaster ride. Brian, do you remember any of that?

 There are several days that I don’t remember. I couldn’t remember my boys’ names and ages. I remember being asked things and I couldn’t respond. It was a weird experience. But again, we did get through it; I wouldn’t want to do it any time soon again. You made it very clear that that was a potential, and sure enough. But we were in a great hospital. We were very well taken care of, so we got through it.

I think we appreciated, too, the sense of urgency. I knew Brian was in good hands because everybody was so caring and took such great care of him. Even going through these challenging and difficult times that everyone had explained to me, I kept saying, “Are you sure this is normal?” because it definitely wasn’t normal to me. But being told that, “Yes, it’s going to be OK,” and being reassured that he would get through it and that it just would take a little bit of time. It was very helpful to me to have that reassurance.

Relapsed DLBCL: CAR-T Cell Related Side Effects

COVID-19 [coronavirus disease 2019] has made it hard for patients and their families because we’re so restrictive as to who can come in the building and who can spend time, though with our patients receiving CAR-T [chimeric antigen receptor-T cell therapy] we make an exception. We want a family member present, and with axi-cel [axicabtagene ciloleucel], we are administering the cells inpatient and then monitoring for these acute adverse effects and keeping the patient in the hospital until they resolve. There is quite a bit of burden, and again, Denise, I want your perspective on this. But we advise you to notify us about any development in toxicity, though we are watching closely as well.

Now there are not staff in the room 24 hours a day, but at least with a change in shift, we require patients to perform some functioning to assess for the neurotoxicity. Any time nurses or staff walk in and there’s concern about changes, again we’ll perform those objective tests to essentially guide or gauge how intense the symptoms are and sometimes intervene.

But I always feel bad for family members because I feel there is this sense that they are watching so closely they don’t want to miss anything. And then as you said, when patients start to feel bad, oftentimes they are treated differently than they normally would, and it has nothing to do with the patient, their brain is not functioning properly. I think you take the brunt of that as well.

And there’s the fear and the concern that this is a loved one, you want them to be normal, and they’re not acting normal. What was your perception of that? Am I on to something?

 Oh, you definitely hit the nail on the head. It was difficult. And because of COVID-19, we couldn’t have family members in. I think maybe there would have even been some groups that I could have participated in as far as having support inside the hospital had it been a normal time.

I definitely had family members who I reached out to and who reached out to me on phone calls, texts. That was my support system because during the times when he was very disoriented and confused and I felt like I was on my own, that support was needed and important to me to handle the difficulty of getting through the situation.

The nurses and staff, everybody was very concerned for me and asking, “Are you doing OK?” Or “How can we help?” I appreciated that care and concern. But many people would say, “Make sure you have self-care,” which is easier said than done. I think you also need that support system. Brian was going through it physically, and I think I was going through it emotionally. I needed some support, love and care from family members and friends. That was very important for me.

CAR-T for DLBCL During COVID-19: A Caregiver’s Experience

Brian, how long were you in the hospital?

 Two weeks. Six days of that I was in the ICU [intensive care unit]. I saw that with the stem cell transplant. You’re very isolated, and it’s the same thing with CAR-T [chimeric antigen receptor-T cell therapy]. It threw me for a loop just how isolated we really were. For patients who are getting ready to go through that, get ready and plan. I didn’t plan very well. I thought I’d just watch Netflix and I’d be fine. But that wasn’t the case.

I did audio books, I tried everything, and I couldn’t find anything that helped me get through that. That was the most difficult thing for me, and I was glad that Denise was able to be there. I would not have survived for sure.

 Denise, do you feel like he was close to having all those symptoms resolved when he left the hospital?

 When we first left the hospital, and we stayed in the area as is the requirement to be monitored closely, he still had some, I would say, mild confusion, or maybe disinterest. If we were watching TV, and it might be on a program that he would never in a million years watch, but he would stare at it, not really with any interest but just not having the want or the desire to change the channel. Or I would say, “Do you want to watch something else?” “No, I’m fine.” But it was very weird. It was strange, to get back to his normal self.

But by the time we left the hospital, I felt like he was getting back to his normal self.

 Yes, and you raise another good point. We do require patients stay within a certain radius for the first four weeks. We recognize that you might be in the hospital one to two weeks, and on average, patients stay for two weeks. Again, that’s because the vast majority of patients will have some form of acute toxicity, and we keep you in the hospital until that resolves.

What was it like between the time you were discharged from the hospital and before you saw me around day 30?

 With talking to me, which we talk a lot and often, about everything, he did not have the discussion or the words. I was worried because I thought he was not his normal self. I definitely noticed changes like that. But some of it may have been due to medication also, which we were told about. It was difficult. It definitely was a process. It wasn’t like we had the treatment, got out of the hospital, and things were just normal. It definitely took some time to regain a sense of normalcy.

 I was surprised at how weak I was, actually. That really surprised me. I had some difficulty getting up and down. But every day it just got better and better. And while I wanted to just sit in a chair, I pushed myself pretty hard and was encouraged to get moving and walking the halls as much as I could, and that helped dramatically.

You have to work at this process. You have to participate and work hard and not give up. But again, the strength came back.

Relapsed DLBCL: Recovering After CAR-T

We generally follow patients a couple times a week, sometimes once a week, depending on laboratory test results or symptoms up until day 30, and that’s an average. Some patients will be seen on day 28, some patients on day 35. But right around day 30, that’s when we have our first response assessment. We also want to see patients to make sure that the acute toxicity has fully resolved or is quite close to resolving, and we don’t have any late problems arising. What was that visit like?

 We did a PET [positron emission tomography] scan, and it was dramatic. Looking at the PET scan was amazing to see how things prior to the CAR-T [chimeric antigen receptor-T cell therapy] really lit up and then just a few weeks later, it was a dramatic change. We were astounded. We didn’t have any idea it would be that dramatic.

 You’re right, you had a complete response on that day 30 PET, which is what we’re all hoping for and super excited to see. And then we let you go home at that point. And what has it been like since you were discharged from our care?

 Great, really great. Again, I feel like I’m almost back to normal as far as energy and strength. My job entails a lot of energy spent during the day. I’m back to normal as far as work goes, and no side effects that I can feel or notice.

 Moving forward, what we counsel patients about is the late toxicity of CAR-T. Essentially we’re going to wipe out all your mature B cells, and that is true for about six to 18 months. That can vary from one person to the next. That can lead to something called hypogammaglobulinemia.

When B cells are performing normally, they make antibodies, so when we wipe out B cells for a temporary period, antibody levels plummet. I’ve had patients who are susceptible to viral infections, including having recurrent viral infections because they don’t build that antibody response.

Outside of COVID-19 [coronavirus disease 2019] times, it’s probably been most notable in my patients who have young children who are generally bringing home viruses. But I would say most patients do very well. It’s particularly nerve wracking in the setting of a viral pandemic. What has that been like for you in the era of COVID-19?

 I’m hypersensitive. I’m very careful about my environment and making sure I’m washing my hands. It’s in the forefront of my mind, really, to be careful and cautious the best that we can. Denise is a teacher, she’s with a lot of “germy” kids, and so we try to be as cautious as we can, but so far so good.

 In addition to things like COVID-19, we advise patients to stay on prophylactic antibiotics and antivirals, so prophylaxis for PJP [pneumocystis jiroveci pneumonia], pneumonia or bronchitis, and then prophylaxis against shingles reactivation. And so that we advise patients to stay on for a minimum of a year, sometimes longer depending on how long it takes for those counts to recover.

We’ve seen some late infections, including infections that happen beyond the first few months, and that can linger for several months into this.

The other thing we’re watching for, and not necessarily at this point in time but over the next few years, is the development of second cancers. That’s a challenging discussion to have. But patients with lymphoma are more susceptible to second cancers.

Fortunately, they’re most commonly basal cell or squamous cell cancers of the skin, so those are the nonmelanoma skin cancers. But we have seen patients who also have melanoma skin cancers. Any solid tumor is a possibility, and then what we worry the most about are treatment-related changes to the bone marrow, something called myelodysplastic syndrome, or even acute leukemia.

These are things that we feel particularly bad about, because we think that you’re on the path to cure, and so we’ll be mindful and watching for second cancers for the rest of your life. But I’m very optimistic that you’re going to do very well.

Relapsed DLBCL: Assessing Response to CAR-T

 Denise, do you have any advice for caregivers of someone who is about to head down the path of CAR-T [chimeric antigen receptor-T cell therapy] or considering it?

 I would say take one day at a time. It’s very easy to jump ahead, especially in the beginning, and you start with all the what ifs. It’s scary, we have three sons, and the youngest was still in high school and the others were in college. You have a lot of fears, fear of the unknown. And then sometimes the fear of the known.

I would say take it a day at a time. Have that support group to help you through and to help encourage you. Also, we were very reliant on our faith to get us through, and I think it’s very important to have the family and friend support to help you through the challenging times and the whole journey.

Hang in there and take it a day at a time. Sometimes maybe a few hours at a time. Don’t be too hard on yourself. Realize that your feelings of being overwhelmed and scared and anxious are all normal feelings. But you can do it, and just do the best you can to take care of yourself and stay positive. Stay on the mission to get healthy and to go through the process of seeking and obtaining remission.

 Brian, you brought up also some good points about staying active and maintaining your physical strength. Any other insights you can share for other patients who are headed down this path or at least considering it?

 Yes, I probably could write a book. But the big thing is you’ve got to be your own advocate with this process. It’s so easy to fall through the cracks. We both tend to be laid back and wait for things to happen, but Denise is constantly calling, saying, “We’ve got to make this appointment, we’ve got to get this ball rolling, we need answers.” Don’t hesitate to be your own advocate. That’s the big one.

It’s true, sometimes it was just taking it a minute at a time. You felt so bad that you thought, “Oh, boy. I’m not sure I can get through this.” Just take it a step, a minute, a day at a time. There’s a lot of hope out there, there are a lot of new treatments. It’s mind-boggling, really, what’s out there. Don’t give up, keep going, and if you get a diagnosis that sounds pretty bleak, find those doctors who know what’s coming, what options you have, and don’t lose hope.

 I can say that both of you are very kind human beings, so it’s not that you’re laid back, you’re just very kind and very easy to work with.

CAR-T for Relapsed DLBCL: Advice for Patients & Caregivers

 Brian was diagnosed and treated near his hometown, and I was contacted after he had failed what we consider standard therapy. He had failed the bendamustine rituximab and R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] and even stem cell transplant. At that point, the next step in the management of his care was either consideration of a clinical trial or CAR [chimeric antigen receptor]-T cell therapy.

There are a number of other agents that have recently been FDA [Food and Drug Administration] approved for the management of large cell lymphoma. But at the time of Brian’s relapse, these were not readily available.

I was contacted by his local oncologist who specifically was interested in consideration of CAR-T cell therapy for Brian. CAR-T cell therapy is something that is administered at a referral or tertiary center, and most of the centers that are administering CAR-T right now are the same centers that administer stem cell transplants, so most of them are FACT [Foundation for the Accreditation of Cellular Therapy] accredited.

There are two FDA-approved products; they differ in terms of their construct, so how they’re stimulated once they engage their target. There’s a third that’s anticipated to be FDA approved, maybe as soon as this month. That one probably has the most favorable safety profile. There are some discussions about whether that construct could move out of the transplant centers and potentially even into community centers, including one where Brian was treated.

But as of right now, most of our patients who are considered for CAR-T, there is a working relationship between the primary oncologist and the referral or tertiary center, such as myself. We generally will identify patients as to whether they’re candidates for CAR-T, request insurance approval, and get them through the collection, manufacturing, cell infusion in the first 30 days.

Once they hit that 30-day mark, unless there is ongoing toxicity, my general practice is to refer them the patients back to their local oncologist, mostly for the convenience of the patient, and also to facilitate a relationship with those primary oncologists who are on the front line seeing all cancer types, and are important to foster that relationship since they’re the ones who are potentially identifying patients who might be referred to us.

Brian is now back under the care of his local or primary oncologist, though we stay in close communication, and he and his local oncologist both know that if there is ever any sign of either lymphoma or toxicity, I’ll be the first phone call. Brian, do you think that’s a fair summary?

 It is. It really is. I’m back with our primary oncologist, and he is doing a great job of keeping track of blood work and laboratory tests and watching me very closely, and he is very encouraging.

Managing DLBCL: A Team Effort

One last question for you. This is a one-time treatment and you’re done. I know it’s early in this course, but I am very optimistic that you’re cured and you can now move on and face other challenges with life. But what are your thoughts about that? Is it too soon to consider that, or are you optimistic?

 We’re cautiously optimistic, I would say. We’ve been down this path where we get such great news and we’re so excited, we call everybody, and then a few months or a year later, it’s back. We are cautiously optimistic. We know that there are so many things out there that are coming down the pike. If diffuse large B-cell lymphoma does happen to come back, we’re not going to give up hope.

I would say the same thing. We often use the term cautiously hopeful. I think we’re still processing and working through; we want to grab onto that assurance that he is cured, and we are finished with that process. It still is a process to work through, I think, because having had the relapse three times, it is a process. But we’re so grateful.

And we have great hope and encouragement now that this one is going to stick and that this is the answer for us.

 Well, I sure appreciate your time, and I appreciate your trust in us in giving up a minimum of four weeks of your life. I know it was much longer than that in the grand scheme of things. And I appreciate you sharing your story for other patients to potentially learn from your experience.

 We are so grateful, and thank you so much for your part in giving him the gift of life, truly. Thank you.

CAR T Therapy for Relapsed/Refractory DLBCL: Brian’s Story