Case Study: UVA Treats First Non-Trial Adult Patient with CAR T-Cell Therapy

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.

Assessed and treated by: Oncologists Indumathy Varadarajan, MD, and Craig Portell, MD

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.