Two men talking in a clinic room
Hematologic malignancies and cellular therapy specialist Ahmed Galal, MD, FRACP, MSc, consults with a patient at the Duke Cancer Institute Blood Cancer Center.

CAR T-Cell Therapy Gains Ground

a boy in a baseball cap and hoodie
Connor McMahon was treated at a children’s hospital in Atlanta for leukemia, first at three years old, then eight years later when he was 12. When he relapsed again at 15 (left), he traveled to Duke for a clinical trial of a first-of-its kind treatment — CAR T-cell therapy. That was in 2016 — the summer before his sophomore year of high school. For the next several months, he and his family would drive up to Durham from Atlanta for weekend follow-up appointments with his care team.

In the summer of 2016, three-time leukemia patient Connor McMahon, then 15, enrolled in a clinical trial at Duke of a novel immunotherapy using his own disease-fighting T-cells. While there was a significant risk of life-threatening complications, the Atlanta teen — under the care of Duke pediatric bone marrow transplant specialists Tim Driscoll, MD, and Paul Martin, MD —came through the trial with flying colors and was declared cancer free.  

In sworn testimony before a U.S. Food and Drug Administration (FDA) panel the following summer, Connor’s father Don McMahon urged the regulatory body  to approve the customized investigational therapy Connor received, a chimeric antigen receptor (CAR) T-cell therapy called Kymriah (tisagenlecleucel). Weeks later, Kymriah became the first commercially available gene therapy in the U.S. when it received accelerated approval from the FDA to treat children and young adult patients (through age 25) with relapsed/refractory B-cell acute lymphoblastic leukemia.

Natural human T-cells, which help orchestrate the body’s immune response, are often fooled by cancer’s disguises. CAR T-cell therapy gives them the boost they need. Unlike a pharmaceutical with a defined chemical formulation, CAR T-cell therapy is made from a patient’s own T-cells (a type of white blood cell called lymphocytes), which are re-engineered in a lab to produce proteins on their surface called chimeric antigen receptors (CARs). These CARs enable the T-cells, once infused back into the body, to recognize and bind to a specific overexpressed antigen (either CD19 or BCMA) on the surface of cancer cells that’s driving their out-of-control growth. The CARs bind with the antigens — like keys into a lock —deactivating those cancer cells. 

Headshot of Krista Rowe-Nichols
Krista Rowe-Nichols RN, MSN, AOCNS

Accelerating Access

Kymriah was not a one hit wonder. A second CAR T-cell therapy, Yescarta (axicabtagene ciloleucel), was granted accelerated approval by the FDA in October that year. Yescarta was approved as a third-line treatment in adults with large B-cell lymphoma, which refers to several non-Hodgkin lymphoma subtypes, including diffuse large B-cell lymphoma (DLBCL).

Duke Cancer Institute, which has been a national trial site for CAR T-cell therapies since 2015, was able to offer both groundbreaking immunotherapies commercially within in a matter of months of FDA approval.

A DCI team prepared the clinical facilities and trained providers and technical staff to meet both the stringent national safety standards set by the FDA and the accreditation requirements set by the Foundation for Accreditation for Cellular Therapy. New workflows, led by Duke Blood Cancer Center clinical nurse specialist Krista Rowe-Nichols, RN, MSN, AOCNS, were developed and implemented.

DCI already had experience in this area, having been a national trial site for not only the Kymriah study, but also for a study (then in progress) of brexucaabtagene autoleucel (Tecartus) in adults with mantle cell lymphoma, an aggressive type of non-Hodgkin lymphoma (Duke site PI: Ahmed Galal, MD).

On Jan. 31, 2018, DCI joined a select group of medical centers across the country certified and trained to administer Yescarta commercially, followed by Kymriah soon after.

Since then, the FDA has approved four more CAR T-cell therapies and has expanded indications in the earlier therapies — all in blood cancers.

DCI is now certified to offer all six commercially-available CAR T-cell therapies that together encompass treatments for:

  • B-cell acute lymphoblastic leukemia;
  • various B-cell non-Hodgkin lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and less common types; 
  • and multiple myeloma.
A person receives a blood product infusion

Stepping Up, Surmounting Barriers

This last fiscal year saw the number of patients undergoing CAR T-cell infusion almost double from the year before.

“We’re seeing the same growth pattern emerge this year,” says Jake Keller, MHA, administrative director of the Duke Blood Cancer Center. “The expansion in commercial CAR T options at Duke has led to it becoming a significant part of our service and future.”

A major contribution to this growth, Keller explained, was the FDA approval of Yescarta in April 2022 and Breyanzi (lisocabtagene maraleucel) in June 2022 as second-line treatments for large B-cell lymphomas. Up to that point, most CAR T-cell therapies were an option only in cases of “double or triple hit” disease (after two or three therapies had already failed to work). Multiple myeloma, meanwhile can’t be treated with a CAR T-cell therapy any earlier than as a fifth-line treatment, though this is currently under FDA review in Abecma (idecabtagene vicleucel).

Another factor driving the increase in CAR T-cell patients at Duke, adds Rowe-Nichols, is the easing, over time, of some of the barriers to accessing this type of therapy.

“When I speak to referring providers who don’t offer CAR T at their facilities, I tell them, ‘Let us worry about the logistics of it. Give us a chance to figure it out and use the resources we have to come up with a solution that works for us, but most importantly for the patient and their family,’” says Rowe-Nichols.

This includes connecting patients with internal and external resources to help pay for treatment as well as mileage, lodging, and meal assistance programs for patients and caregivers, which most insurance companies won’t cover.

“Duke is unique in terms of our managed care department and some of the additional layers of financial authorization approvals we go through, beyond the insurance authorizations,” explains Rowe-Nichols. “We do all we can to protect our patients from financial risk.”

Team Effort

Seven years ago, CAR T-cell therapy was experimental. It was a high-risk and potentially high-reward type of treatment.

It remains high-risk, but treatment toxicities are now better managed as clinicians have gained more experience with CAR T and the administration of supportive therapies. Each CAR T product the Blood Cancer Center administers has their own FDA-approved Risk Evaluation and Mitigation Strategy Program for which the Blood Cancer Center must be certified.

“The most important thing is that we intervene early, and that our patients get the medications they need to manage the side effects, whether in our main clinic or hospital in Durham,” says Rowe-Nichols, stressing that patients and their caregivers are required to stay close by (30 minutes to an hour away per DCI rules) for at least 28 days and in some cases up to five weeks. “We don't have a crystal ball of knowing who's going to get certain side effects and who won’t. What I can assure patients is that everybody that's here knows how to recognize even the worst side-effects, such as cytokine release syndrome (CRS) and neurotoxicity, and are well equipped to deal with them when they happen…”

It takes an entire team, including many people behind the scenes, to make sure the patient experience with the complexities of CAR T-cell treatment goes smoothly.

“I think of our Stem Cell Lab and our Apheresis teams, who have the herculean and critical task of collecting, handling, freezing, storing, tracking, and thawing the blood products (in various stages of this process) as the Santa’s elves of our efforts,” says Rowe-Nichols. “We could never do what we do without them.”

young man holding a sign in a yard that reads "7 Years Cancer Free" with a red ribbon
Connor McMahon, 22, is now seven years cancer free. Following his second battle with leukemia at age 12, he came up with an idea to give back to kids with blood cancers who had to stay at the hospital for months at a time. To make those long stays easier, he launched Connor’s Hope (http://Facebook.com/ConnorsHope30). A few times a year, he and his mother, father, brothers, and hockey teammates would make special deliveries — gift bags with games, pencils, coloring books, and crayons — to young patients in Atlanta. Currently a senior at Florida Gulf Coast University pursuing entrepreneurship, he’s connecting with area children’s hospitals for another delivery soon. (photo courtesy Connor McMahon, October 28, 2023)

Keeping Up With Studies, Fighting Resistance

The potential for long-term remission has become clearer since the first CAR T-cell therapy clinical trials began, but it’s still early days. There’s published data on Yescarta for example, that fewer than half of patients survived five years post-treatment, but for those who did, most didn’t require further cancer treatment. 

The Duke Blood Cancer Center is currently participating in a multi-institutional 20-year long-term follow-up study (safety, effectiveness, and prolonged action) of 700 patients who participated in Kite-sponsored clinical trials of Yescarta, Tecartus, and five other Kite therapies. It commenced in 2021 and will end in 2041. 

Connor McMahon, the teen whose participation in the Kymriah study at Duke garned national media attention from The New York Times and Good Morning America, among others, is now 22 and out of the limelight. The senior in college is seven years cancer-free. He hasn’t had any residual side-effects from treatment. Since the trial ended, however, he’s had to have two subcutaneous injections a week. According to Paul Martin, MD, PhD, those shots are immunoglobulin replacement therapies.

“One of the major side effects of CART therapy is that we destroy the good and the bad B-cells so he can’t make his own antibodies. The injections provide antibodies from several hundred volunteer plasma donors,” explained Martin, who continues to see patients at Duke Children's Hospital & Health Center Bone Marrow Transplant Clinic. “The major risk is non-compliance. Most CAR T patients do need this replacement therapy for some period of time and those patients who receive Kymriah often need it for life.” 

In fact at one point, when Connor got off schedule with the shots, he contracted serious pneumonia.

Connor and his dad keep in touch with Martin for whom they are grateful. “Spending that much time together and doing something so big together, we've become friends in a way,” said Connor.

Hematologic malignancies and cellular therapy specialist Ahmed Galal, MD, FRACP, MSc, calls CAR T-cell therapy “a gamechanger.” “It’s going to turn a disease for which we've never mentioned the ‘C word’ — cure — into something that we are sort of entertaining now.… And when success happens, that's it. I mean, what else you can wish for?” 

And when it doesn’t? One of the biggest challenges in blood cancers and all cancers is treatment resistance. Duke is currently participating in clinical trials seeking to mitigate this resistance, including:  

Preclinical (lab) studies at Duke are also making headway on the resistance issue, says medical director of the CAR T program and Director of the Kang Lab, Yubin Kang, MD.

“We were awarded a National Cancer Institute grant about 1.5 years ago to do research … to understand the mechanisms of resistance and how to overcome them,” said Kang, adding that some early results were presented this fall at the Duke Immuno-Oncology Program & Center for Cancer Immunotherapy 2nd Annual Scientific Retreat by postdoctoral associate Xiaobei Wang, PhD, and by 4th year medical student Parker Matthews. 

The Long Game, Promise of Immunotherapy

CAR T-cell therapies are only one slice of the immunotherapy pie. Immune-based therapies, including cancer vaccines, stem cell transplants, cord-blood based cell therapies, monoclonal antibodies, engineered T-cell therapies (TCRs), chimeric T-cell therapies, and tumor-infiltrating lymphocytes, are all in various stages of development, testing, and deployment at DCI's Center-for Cancer Immunotherapy

The broader cancer-fighting story continues.


Learn More

The Duke Blood Cancer Center, which saw nearly 2000 total patients last fiscal year and is on track to eclipse that this fiscal year, is a go-to destination for patients in North Carolina and beyond seeking blood cancer treatment. 

Patients who are interested in being evaluated for CAR T-cell therapy must have their physician provide a referral. To refer a patient for an evaluation to determine the best treatment option, please call 919.684.8964.

Duke was the first center in North Carolina to offer FDA-approved chimeric antigen receptor (CAR) T-cell therapy. This personalized immunotherapy can be used to fight specific forms of lymphoma and leukemia when other treatments like chemotherapy have proven ineffective. Here, Ahmed Galal, MD, a hematologic oncologist at Duke Health, explains how CAR T-cell therapy works and answers common questions about this "game-changing" cancer treatment.
This page was reviewed on 01/24/2024