At a Glance:
- CAR T-cell therapy is now FDA approved for use in adult patients with refractory and relapsed lymphoma
- UVA recently treated its first non-trial adult patient with CAR T-cell therapy
- Case study highlights steps involved in CAR T therapy and patient's successful outcome
- UVA recently opened the Center for Human Therapeutics, a new cGMP facility that will allow them to engineer some CAR T cells on site
Over the past decade, UVA researchers have led the way in advancing a type of immunotherapy called CAR T-cell therapy with their involvement in hallmark clinical trials. Because of promising outcomes from these studies and others, the U.S. Food and Drug Administration has now approved CAR T therapy for use in patients with adult aggressive B-cell lymphomas and pediatric and adolescent B-cell leukemia whose cancer has not responded to two standard prior chemotherapy treatments.
UVA Health recently treated its first non-trial adult patient with CAR T-cell therapy. Learn more about the treatment process and this patient’s outcome in the case study below.
Case Study: CAR T-Cell Therapy
Patient: Steve Chiminello, 69-year-old male
Presented with: non-Hodgkin lymphoma
Chiminello was diagnosed with non-Hodgkin lymphoma in 2017 by his local oncologist. In just a year’s time, the cancer morphed from mild and manageable to a more aggressive form of the disease. “I thought we were going to be able to take care of it. I had a few treatments and went into remission. But four or five months later, it came back and it had transformed into something different from my initial diagnosis,” says Chiminello.
Out of treatment options, Chiminello’s oncologist referred him to UVA Cancer Center.
Treatment: CAR T-cell therapy
“CAR T-cell therapy was just approved by the U.S. Food and Drug Administration for commercial use in adult patients with refractory and relapsed lymphoma. That is cancer that has not responded to two prior forms of chemotherapy,” says Varadarajan. “I felt Mr. Chiminello was a good candidate because of the nature of his disease and because he was fit and healthy overall.”
“Dr. Indu – that’s what her patients call her – did a wonderful job presenting the treatment options,” says Chiminello. “But I was tremendously apprehensive at first.”
Chiminello sought a second opinion from doctors at University of Pennsylvania Abramson Cancer Center, the birthplace of CAR T-cell therapy. What he discovered was that UVA and Penn Medicine were longtime collaborators in the effort to advance this promising treatment.
“One of the forefront clinicians leading a lot of the CAR T trials is in close collaboration with us and we have frequently referred back and forth. We’ve sought his advice on various clinical cases and he has been a great resource for us,” says Varadarajan.
The knowledge of this partnership – and his trust in Dr. Varadarajan and Dr. Portell – gave Chiminello the confidence he needed to move ahead with treatment close to home at UVA.
The first step in the treatment was harvesting his body’s T cells. His blood was processed through a dialysis-like machine. T cells were extracted and the blood was returned to the body. Collected T cells were then sent to a facility where they were inserted with a gene that has a chimeric antigen receptor (CAR). The CAR essentially reprograms the T cell so that it seeks out a particular cancer cell and destroys it.
While his T cells were being processed, Chiminello had intense chemotherapy for three days to weaken his immune system, which helps ensure the body won’t attack the newly introduced CAR T cells before they can do their job.
The T cells were then reinserted intravenously. “The process took about 20 minutes and there was no pain,” says Chiminello. “At that point, it was just the psychological stress that took its toll.”
Recovery: minimal side effects; two-and-a-half weeks inpatient care, followed by a week-and-a-half of outpatient monitoring
Injecting the body with a huge influx of hyperactive immune cells is risky, and can cause side effects. The immune system responds as if you have a bad infection, so symptoms are much like an incredibly bad case of the flu: fever, body aches and fatigue. This is called cytokine release syndrome (CRS). Although this extreme immune response is welcome and necessary, Chiminello was admitted to the hospital to ensure symptoms were kept in check.
“The doctors had spelled out all of the side effects for me, so I was prepared,” says Chiminello.
Fortunately, Chiminello did not experience the extreme side effects he’d be dreading, only a low-grade fever, which was actually a good indication that the therapy was working.
Outcome: zero complications and clean scans
Chiminello is a CAR T success story. And he’s helped provide UVA with a roadmap for administering this new treatment to more patients.
“His experience was very important for our staff. It helped us understand how to manage these patients, how to prepare for different side effects and, to be honest, it gave both our inpatient and clinical staff confidence,” says Varadarajan. “We know we can do this and do it well. We are able to produce the same results as some of the larger centers.”
Chiminello also set an example for patients to follow. “He’s helped a lot of other patients,” says Varadarajan. “I have one or two who are getting the therapy and they’re very excited and happy for him that he’s still in remission. In that way, he is an inspiration.”
Looking Ahead: Car T-Cell Therapy at UVA
CAR T-cell therapy is promising, yet is relatively new. The first adult lymphoma patient was treated in 2009 and the first child with leukemia was treated in 2012, so more time is needed to evaluate long-term effectiveness. While we know that complete remission or elimination of cancer is possible for some patients treated with CAR T-cell therapy, we also know it’s not a cure for everyone. Understanding how we apply this therapy and modify it to help more patients is a critical step forward in advancing cancer treatment.
At UVA, steps are being taken to ensure resources are in place to make progress possible for CAR T-cell therapy. UVA recently opened the Center for Human Therapeutics, a new cGMP facility (a facility that meets the current good manufacturing process standards set by the FDA for places that manufacture pharmaceuticals) that will be the only one of its kind in the state of Virginia.
The facility will include the space and technology necessary to engineer some CAR T cells on site, including the next-generation CAR cells currently being used in clinical trials for both adults with lymphoma and children with leukemia, as well as children with brain tumors, a brand new area of study. With production on site, the wait time for processing and shipping of these enhanced cells will be drastically reduced, giving more patients access to a potential cure.
To refer a patient to UVA Cancer Center, call UVA Physician Direct at 800.552.3723.