Keynote Session: Experience With Innovative Therapies

A Focus on CAR T-Cell Therapy

The use of innovative treatments such as chimeric antigen receptor (CAR) T-cell therapy is rapidly expanding. The challenges of receiving and delivering this novel therapy were discussed at the NCCN 2019 Annual Conference’s keynote session. In a separate roundtable discussion, additional stakeholders discussed how payers and providers are grappling with the cost of incorporating CAR T-cell therapy into practices.

Abstract

The use of innovative treatments such as chimeric antigen receptor (CAR) T-cell therapy is rapidly expanding. The challenges of receiving and delivering this novel therapy were discussed at the NCCN 2019 Annual Conference’s keynote session. In a separate roundtable discussion, additional stakeholders discussed how payers and providers are grappling with the cost of incorporating CAR T-cell therapy into practices.

The use of innovative treatments such as chimeric antigen receptor (CAR) T-cell therapy is rapidly expanding. More centers are developing dedicated programs for the delivery of this therapy, but in its early days, the learning curve could be steep. The challenges of receiving and delivering this novel therapy were discussed at the NCCN 2019 Annual Conference’s keynote session. In a separate roundtable discussion, additional stakeholders discussed how payers and providers are grappling with the cost of incorporating CAR T-cell therapy into practices (for more on the NCCN Roundtable, “Emerging Issues in Oncology,” see https://www.nccn.org/about/news/newsinfo.aspx?NewsID=1512; video is available at https://youtu.be/z9qG_8ue6jM).

Sharing perspectives on CAR T-cell therapy at the NCCN 2019 Annual Conference were Jeffrey Backer, MD, a doctor at Emergency Physicians of Central Florida and who was also a patient, and 2 members of his treatment team at Moffitt Cancer Center: Frederick L. Locke, MD, Vice Chair and Associate Member of the Department of Blood and Marrow Transplant and Cellular Immunotherapy, and Alix Beaupierre, BSN, RN, OCN, Blood and Marrow Transplantation and Cellular Immunotherapy Nurse Coordinator.

Dr. Locke also participated in the discussion of costs in an NCCN Roundtable moderated by Clifford Goodman, PhD, Senior Vice President at The Lewin Group, a national healthcare and human services consulting firm. Dr. Goodman elicited perspectives as well from John W. Sweetenham, MD, Executive Medical Director and Senior Director for Clinical Affairs at the Huntsman Cancer Institute at the University of Utah; Lalan S. Wilfong, MD, Executive Vice President for quality programs and value-based care for Texas Oncology and physician liaison for value-based care for McKesson Specialty Health; Stefanie Joho, research/patient advocate and consultant; and Jennifer Malin, MD, PhD, Senior Medical Director of Oncology and Genetics at United Health Group.

CAR T-Cell Therapy for Diffuse Large B-Cell Lymphoma

Dr. Backer recounted his encounter with CAR T-cell therapy and its treatment. His cancer journey began in 2014 when he developed symptoms that led to his diagnosis of diffuse large B-cell lymphoma. This often-lethal cancer was made even more foreboding, in his case, by being the aggressive double-hit variant. His local hematologist told him, “‘I can get you into remission, but the question is whether I can keep you in remission’,” he said. “That stuck with me.”

After undergoing standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) plus ibrutinib, he did attain a complete response and was able to return to work. However, a month later, he experienced relapse.

Successes from additional treatments were short-lived and his prospects for long-term survival were diminishing when in June 2017 he enrolled in the ZUMA-1 clinical trial of axicabtagene ciloleucel (axi-cel) at Moffitt Cancer Center, with Dr. Locke as his treating physician. His prospects for survival changed, but looking back, he realizes he was “totally unprepared for CAR T.”

“Like a Nuclear Bomb”

Dr. Backer described the CAR T-cell therapy experience as different from other tough situations he had experienced. He developed cytokine release syndrome (CRS), which he described as “a nuclear bomb set off” in his body. The workup for his CRS had a serendipitous outcome, however. A CT scan performed to detect possible infection revealed that in 1 week’s time he was disease-free. He recovered from the CRS and remains disease-free 33 months later.

Noting that the posttreatment course can be “rocky” for many patients, Dr. Locke advised that, “we as a healthcare team have to come together to help our patients through that journey.”

“For me, CAR T was a miracle treatment,” Dr. Backer told the audience. “I knew that with the double-hit lymphoma, my chances of survival long-term were close to zero. It just worked out for me. The last thing I would have expected would to be to sit in front of an NCCN audience telling my story.”

Managing CAR T-Cell Therapy 2 Years Later

Centers such as Moffitt have learned a lot about delivering CAR T-cell therapy from experiences such as Dr. Backer's and have instituted protocols quickly and effectively, according to Ms. Beaupierre. As a nurse coordinator overseeing these treatments at Moffitt, she acknowledged that, just as Dr. Backer was unprepared for the CAR T-cell therapy process, she and her staff were as well. They are now much better equipped, she said, “to help provide a seamless journey through all the services we provide.”

She said that patients and their families are most in need of certain things from the care team: a simpler informed consent form, better preparation for the CAR T-cell therapy process from start to finish, a dedicated care team leader to guide them through this process, and specific information about CRS and neurotoxicity. It is the responsibility of the cancer center to ensure these things for patients.

How Moffitt Learned, and Improved

One of the first signs that early patients and their families were not getting what they needed came in the form of distress the nurses witnessed. “We were receiving ‘911s’ from our in-patient department. They were saying that patients and caregivers were in distress because they were not prepared to witness the patient’s experience, especially with CRS, with 105° fevers, and patients wrapped in ice and bear huggers, not to mention the neurotoxicity,” she said.

Patients and caregivers also seemed overwhelmed by the 27-page informed consent document. “You, Dr. Backer, and many other patients just want to sign it [without understanding it] because you have active disease and you want it treated,” Ms. Beaupierre said.

The care team’s response was to “quickly get our patient education department together with our clinical trial coordinators, nursing leadership, clinical nurse specialists, social workers, and physicians, and see how we could address our patients’ needs.”

The group determined their first step should be to create an education program to prepare patients and loved ones for “the shock of CRS” and neurotoxicity, as well as the prolonged process of apheresis. To this end, they created 1-page handouts that they eventually refined into flow diagrams. They also developed supplemental information for individuals who wanted more. “It’s now grown to a detailed calendar that the patient receives the day of consult,” Ms. Beaupierre said.

As a “best practice,” Ms. Beaupierre evaluated the success of this intervention, asking patients and families if the handouts helped prepare them to manage and support the patient and to understand the treatment. “The feedback was very positive,” she said.

In addition, Moffitt assigned a dedicated nurse to be the patient/family contact throughout the pre- and post-treatment journey. A dedicated advanced practitioner also now meets with all the patients intermittently to address symptoms and needs, and Moffitt holds a pre–CAR T-cell treatment class for patients.

“We’ve all become experts in taking care of the patients and we teach them what to expect,” she said. With these interventions in place, she added, the patient experience has improved since Dr. Backer’s experience.

Peer Support

“I think my experience would be dramatically different today,” Dr. Backer agreed. “I think for me, one other thing that would have been incredibly helpful would be to be able to contact someone who had gone through this, let’s say someone in my demographic and my profession.”

“That’s a very good point,” Ms. Beaupierre responded. “That is actually a long-standing practice with our transplant patients that we have started to implement with our CAR T-cell therapy patients,” Each patient has a dedicated social worker who partners with the nurse to connect patients and survivors.

Dr. Backer is serving as a peer counselor himself for another physician who is undergoing CAR T-cell therapy. “He needed to hear from somebody who’s gone through it—somebody who does what he does—that there’s life after CAR T. That I’m back at work. That once you get over this hump, if you get over it successfully, you’re done. Your cancer is over. There are not a lot of treatments out there where you can say this.”

Where Are All the Eligible Patients?

As Dr. Locke pointed out, Dr. Backer was not the usual patient. He knew how to research his condition and find a clinical trial that could be suitable. “We as a community shouldn’t necessarily expect our patients to go out and seek that,” he said.

He then posed a question to Dr. Backer: “What can we do to increase referrals? Because my impression is, and by actually looking at the numbers, we are not being referred all the patients who are eligible for CAR T-cell therapy. What could we be doing?”

Dr. Backer responded that venues such as this keynote session, “where we are discussing how innovations are being brought into the mainstream,” are a good way “to get the word out to the oncology community.” He added, “As successes diffuse into the community, I think there will be less reluctance to refer.”

“I totally agree,” Dr. Locke said. “The fact that you came to us and your treatment worked has led to additional referrals,” he reported. “I imagine that, one at a time, we can increase referrals through these success stories.”

Continuum of Care

The speakers emphasized that life after CAR T-cell therapy involves oncologists in the community. “A lot of care is required and that is being provided by my oncologist in Orlando,” Dr. Backer shared. “It’s important for everyone to know that while an NCCN center may be providing the therapeutics…if you don’t engage your local oncologists, it’s not going to work.”

Community oncologists may need assurance that referral for CAR T-cell therapy does not mean relinquishing one’s patient, Ms. Beaupierre added. “At Moffitt, we have worked hard to encourage early referrals because we believe it results in better outcomes for the patient, but we’ve also tried to keep the doors of communication open because we need collaboration with community oncologists,” she said.

Her staff instituted a communication process and developed a discharge information packet for the patient to hand deliver to his/her primary oncologist. The treating physician at Moffitt also typically confers with the local oncologist via telephone or email.

NCCN Roundtable: A Wealth of Innovations

CAR T-cell therapy is one example of the innovations occurring at a rapid pace in oncology, the roundtable panelists said. “We have this whole panoply of innovative therapies coming along with entirely different mechanisms of action, new delivery models, and sometimes impacting the site of care. But these are also prompting changes in how we think about paying for these things. Innovation is that pebble in the pond that has very broad implications,” Dr. Goodman commented.

One ramification that cannot be ignored is the issue of cost of care. “What’s missing here is an actual mechanism to pay for this,” Dr. Locke pointed out.

The physicians estimated the cost of CAR T-cell therapy to be between $500,000 and $1.5 million, depending on the specific needs of the patient. “If it’s a complex clinical course with admission to the [intensive care unit], it could go significantly higher,” Dr. Sweetenham noted.

But perhaps “the juice is worth the squeeze,” Dr. Locke suggested. “I think $1 million is a lot, but if we are curing perhaps 40% of patients, then maybe that cost is reasonable,” he said. “What’s the cost of continuing chemotherapy until patients are hospitalized and then end up on hospice?”

But the cost of the drug is not the only factor, Dr. Malin pointed out. The actual payout by the insurer is several times the drug cost. “We reimburse the hospital and the practice typically at some margin above the cost of product,” she said. “The margin approach may make sense when we’re talking about doxorubicin, but we are talking about innovative new therapies that are very expensive. So an elephant in the room is, what is a reasonable profit margin on administrating a drug?”

Dr. Locke commented that reimbursing several times the half-million-dollar cost of the drug is not reasonable, “but an infrastructure is required for CAR T-cell therapy—ancillary staff are necessary to deliver the care, and these costs are hard to quantify,” he maintained. “It’s one thing to say, ‘CMS, pay for this,’ but it’s another to actually pay. The current process for paying does not allow a way for Medicare to actually reimburse enough for the hospitals that are giving this therapy. We can only do this for so long when we are not getting fully paid.”

Treatment centers therefore assume much of the financial risk upfront. Dr. Wilfong said his group, Texas Oncology, is not yet performing CAR T-cell therapy on Medicare patients, because adequate payment is not assured. “As a community-based practice, we don’t have additional sources of revenue that some academic medical centers have.”

“Our center is doing it for Medicare patients, and I think we’re at a huge risk,” Dr. Locke said. “If this doesn’t get figured out soon, we will not be able to continue giving these treatments to Medicare patients.”

The group agreed that a new reimbursement structure for CAR T-cell therapy will be needed to satisfy all parties. “This is certainly a disruptive technology,” Dr. Goodman concluded. “It’s disrupting the current reimbursement system, which doesn’t work for that purpose.”

Toward a National Coverage Decision

The other challenge for the healthcare system is the lack of consistency in coverage for CAR T-cell and other emerging therapies. Today, with any new therapy, CMS lacks a national coverage determination, leaving coverage decisions to local Medicare carriers.

United Health Group recently submitted a request to CMS that it make a national coverage decision, one of the primary aims being to assure consistent access for patients and “equity of assets,” Dr. Malin said.

Disclosures: Dr. Backer has disclosed that he has no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Dr. Locke has disclosed that he has served as a scientific advisor for Kite/Gilead Sciences, Inc. and Novartis Pharmaceuticals Corporation and has received consulting fees from Cellular Biomedicine. Ms. Beaupierre has disclosed that she served on the product/speakers bureau for Kite Pharma. The remaining participants have no disclosures.

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