Immuno-Oncology Resource Center
Immuno-Oncology Resource Center
October 10, 2019
10 min read

Hope vs Hype: Managing Patient Expectations for CAR T-Cell Therapy

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Imagine a young adult male in his late 20s picks up his cell phone and calls his mother. Overtly emotional and on the verge of releasing a full-out flow of tears, the young man says to the voice at the other end of the line, “Mom, there’s hope.”

It’s enough to make an onlooker get emotional themselves, and it comes at the end of what the viewer knows is a 60-second commercial from Penn Medicine, during which a narrator touts the FDA’s approval of CAR T-cell therapy as “one of the most important breakthroughs in the fight against cancer, and this is just the beginning.”

Not once does the narrator say the term CAR-T, or cell therapy, or make any mention of exactly what the FDA approved. Instead, the messaging includes alternating images of relief, hope and celebration. At the end, it refers viewers to a website where they can begin their education about CAR T-cell therapy.

And why would you not read about this “most important breakthrough” in fighting a disease that touches nearly all of our lives, whether it be personally or professionally? Perhaps unlike any other development in cancer treatment, the fanfare and media attention around CAR T-cell therapy has patients asking about details for a new treatment by name, because they’ve seen it on the news, or they saw it on television, or they heard it on the radio.

Hope is a wonderful thing, but hope can also be a dangerous thing. Lack of hope can lead to despair, and few battles are ever won from behind a black cloud. Too much hope can be equally as crippling when patients become susceptible to inflated expectations and ignore the reality of the situation they are facing.

The ability to balance the hope vs. the hype of cutting-edge treatments poses one of the trickier balancing acts facing clinicians. After speaking with experts who themselves treat patients undergoing CAR T-cell therapy, Cell Therapy Next learned that clinicians need to be straightforward with patients about the effects and potential results of treatment while still managing to nurture the pathway that keeps hope alive in a group of patients who have known nothing other than disease relapse and treatment failure.

Straight to CAR T Cells

There has a been a tremendous amount of enthusiasm and patient interest in CAR T cells, according to Brian T. Hill, MD, PhD, director of the lymphoid malignancies program and a staff physician at the Cleveland Clinic. Hill sees patients who undergo CAR T-cell therapy both as part of Cleveland Clinic’s clinical trial programs and as a part of standard-of-care practice and said he believes the hype over CAR T-cell therapy relates to the novel method involved in the treatment approach.


He said patient expectations about the treatment’s effectiveness must be tempered to deal with this hype.

Hill told Cell Therapy Next, “One of the inquires we get is can we do CAR T-cell therapy for a disease that’s not currently indicated, or for earlier lines of therapy?” He also said that patients ask if they can skip traditional therapy and go right to CAR T-cells.

There is a wealth of education required for both patients and their family members once they decide on the CAR T-cell therapy option, according to Hill.

“They may be under the impression that this is a simple one-and-done treatment with minimal toxicity, and that is not the case,” he warned.

First, clinicians need to explain whether lymphodepletion chemotherapy will be required 3 days before the CAR T cells are given.

Then a conversation with the patient and their family regarding the possibility of neurotoxicity must ensue.

Brian T. Hill

“It’s fairly common for patients to become confused, aphasic, sometimes for several days,” Hill said. “This can be quite frightening to loved ones and care givers because they can appear like stroke-like manifestations. They should be prepared by being told that their loved ones may not be responsive and require intensive care after the treatment is given.”

Imparting this education ahead of time is critically important, Hill explained. “It helps make the treatment process go more smoothly.”

As for the treatment’s efficacy, Hill said that commercial CAR T cells for large B cell lymphoma have a very high overall response rate, but that less than 50% of patients will have a durable response to treatment.

“This means that despite all the hype, over half of the patients who undergo CAR T-cell therapy will not be cured of their disease,” Hill said. “This can be a very frustrating part of the experience, and it is part of my job to manage these expectations — to explain that this treatment is not certain to lead to durable remission.”

Community-based CAR-T

Courtney Bellomo, MD, of New York Oncology Hematology, sees patients as part of her private, community-based oncology practice in northern New York. One of her main goals is to bring CAR T-cell therapy to her region as part of her practice’s community oncology program. She hasn’t administered CAR T cells herself, but she has referred patients to larger centers in Boston and New York City and she resumes follow-up care for patients after they return to the community setting.


Bellomo believes that CAR T-cell therapy presents a promising opportunity for many patients and should be given as an earlier line of therapy. She currently refers patients to clinical trials as well as commercial treatments where indicated.

“I constantly think about whether a patient would be a good candidate for CAR T-cell therapy trials, perhaps more often than others in my field,” Bellomo told Cell Therapy Next.

Courtney Bellomo

Bellomo said that despite the media hype, she is the one who more often brings up the possibility of CAR T-cell therapy with her patients. Most of her patients have heard of it, but Bellomo said that most are not sure if the treatment is appropriate for them.

“I would say that about 30% of patients or their family members bring up CAR-T to me and about 75% of those people don’t understand that CAR-T may not apply to them.”

Bellomo believes in a straightforward approach when it comes to discussing CAR T-cell therapy’s efficacy with patients, and she is armed with the numbers.

“I’m a straight shooter. I try to prepare patients pretty well, so I will give them the percentages,” she said. One of those important percentages is understanding that about 40% of patients will relapse after CAR T-cell therapy.

Most people take notice of the cautious optimism during that conversation, Bellomo said, but they still arrive back in her clinic in a state of disbelief when their disease is relapsed and ask, ‘how did this happen?’ This was especially true when CAR T-cell therapy was used only as third-line therapy, Bellomo explained, but now it is being used as second-line therapy in clinical trials.

She said that currently only one of the six patients who received CAR T-cell therapy under her care have survived to this day, and all the others died from relapsed disease.

There is a difference in how she manages expectations depending on the patient’s diagnosis, she said. A patient with myeloma may be incredulous over a projected remaining lifespan of 10 to 15 years, but she said you have to explain to them that there are things in the pipeline that will change the treatment paradigm for this disease in the years to come.

“On the other hand, when a patient is about to receive something like CAR T-cell therapy, we shouldn’t paint it as a cure-all because there is a risk in managing patient expectations,” Bellomo said. “CAR-T may be much better than other treatment options available, but you have to explain to the patient that it may not work for them. There needs to be a definite balance between hope and response rate.”


Bellomo said it’s important to give patients an accurate assessment of CAR T-cell therapy’s effectiveness.

“I think the best thing is to go over the outcomes percentages with patients thoroughly and not paint this treatment as the best thing since sliced bread,” she said. “Although it is a huge advancement in technology that allows us to help people live significantly longer, it won’t fix everyone, and sometimes we forget that — I know I do.”

Examining the Process

Patients are often the first to bring up the possibility of CAR T-cell therapy to Ryan D. Cassaday, MD. He is a CAR T-cell veteran with appointments as a clinical physician at the Seattle Cancer Care Alliance, an associate professor in the division of hematology at the University of Washington School of Medicine, and is an assistant member of the clinical research division at Fred Hutchinson Cancer Research Center. He’s part of a team that has provided CAR T-cell therapy to more patients than any other center in the world.

Cassaday said patients approach him with interest who have diseases that are not yet approved indications for CAR T-cell therapy, such as myeloid disorders.

Ryan D. Cassaday

“Sometimes when I plan to talk about CAR T-cell therapy, the patient will beat me to the punch,” he said. “And even in areas where CAR T cells are not being used, patients will ask if the treatment is an option.”

Cassaday thinks there is a lot of optimism about CAR T-cell therapy, perhaps mostly because there is a wealth of information about it and coverage available via the mainstream press.

“We are more apt to talk about the successes of treatment rather than the failures, and the unfortunate reality is that these therapies don’t work for everyone for a number of reasons,” he asserted. “There is some amount of walking back of patients’ expectations about not just the success rates, but also how long it takes to get plugged into the treatment and how long they may have to stay in a hospital.”

Providing the patient with a lesson on the biology behind CAR T cells and an overview of the entire process is how Cassaday approaches the subsequent conversation about expectations and how to temper those in the face of patient enthusiasm. He takes the time to explain how the cells are prepared, some of the underlying biology, and the subsequent steps in the overall process.


That provides a useful framework to then explain that the patient must come to the clinic and have cells collected by apheresis, and wait for those cells to be manufactured — which can take a couple of weeks.

“With a little bit of background about how the process unfolds and the underpinning biology, it helps patients have a better understanding of why this treatment takes so long on the front end,” Cassaday said.

He then moves on to the treatment itself and what happens once the cells have been infused into the body. “Having patients understand that these cells are designed to live in your body and respond to certain stimuli can create a framework to then talk about some of the more serious side effects with this treatment,” Cassaday said.

Clinicians must explain to patients that there are things they know may occur, but the mechanisms behind who, when and why are not certain — for example, cytokine release syndrome. Another is neurotoxicity, and as Cassaday noted, “there is a lot that we don’t understand, and it can be difficult to know who will or will not suffer from these problems.”

This part of the discussion about the overall process helps provide useful background information and emphasize how much is unknown about the treatment process and how much of it is unexpected, Cassaday added.

“As for efficacy, I usually try to just stick to the data that are available from prospective trials or retrospective analyses from large centers that have done a large number of these treatments,” he said. “You have to emphasize that while many patients will go into remission, many will not experience durable remissions.”

It’s Just the Latest ‘Big Development’

Leslie L. Popplewell

Mainstream news coverage of CAR T-cell therapy continues, even 2-plus years after its first FDA approval. Leslie Popplewell, MD, is an associate clinical professor in the department of hematology and hematopoietic cell transplantation at City of Hope’s Toni Stephenson Lymphoma Center, and this increased awareness about a ground-breaking development in cancer treatment is nothing new to her.

“As with any new therapy, we get a lot of inquiries about how it fits into the patient’s treatment plan,” she told Cell Therapy Next. “Anything with the word ‘cancer’ in it that makes a big splash in the news is going to generate a lot of queries for treating physicians.”

In a familiar refrain, Popplewell said her strategy for managing expectations begins with an honest and up-front discussion about the risks vs. potential benefits of CAR T-cell therapy. The risks will always include discussions about CRS, neurotoxicity and potential complications with lymphodepleting chemotherapy.


“As for the benefits, you just have to be upfront about those,” Popplewell said.

She puts down a few familiar numbers to remind patients: a 40% to 50% rate of complete remission for patients with relapsed or refractory diffuse large B cell lymphoma. She also mentions one follow-up study that shows an 86% ongoing complete remission rate after about 2 years.

“From what I can tell so far, we haven’t hit a home run with CAR T cells, so I think it’s important to let patients know that we are working on ways to make CAR T cells better than they are now,” she said. “We have commercial products on the market now, but that does not mean they are the final form CAR T cells will take.”

Preparing patients for the treatment itself should seem familiar to many patients with relapsed or refractory disease, Popplewell said. “We walk them through the sequence of events, and because a lot of them will have had a previous autologous stem cell transplant, I usually let them know that the process will seem very familiar to them, and many of the risks are similar.”

She also said that involving family members into the education about treatment-related side effects can be helpful because neurotoxicity can sometimes be seen more easily by family members, who are more likely to pick up on subtle signs than medical staff.

“Every few years there is a big development that comes along that raises expectations, so we will need to deal with this periodically,” Popplewell said. “All we can do is tell patients what we know, what we can expect, and what we don’t know and that’s about as much information as we should give. Speculating about what will happen 5 years down the road isn’t very responsible.” – by Drew Amorosi


Disclosures: Cassaday reports research funding from Amgen, Pfizer and Kite and honoraria from Amgen and Pfizer. Hill reports funding from Novartis/Kite and consultant roles with Juno Therapeutics and Novartis/Kite. Bellomo and Popplewell report no relevant financial disclosures.