Twelve adults with chronic lymphocytic leukemia (CLL) have been treated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy at the University of Pennsylvania in Philadelphia by Carl June, MD, Richard W. Vague Professor in Immunotherapy, and colleagues. These were all end-stage patients with no other good treatment options. Thus far, 9 of the 12 patents have had a good response; 3 are in complete remission, with durable responses.
At the recent Annual Meeting of the American Association for Cancer Research, the adult CLL patient with the longest remission to date spoke to attendees about his experience with the therapy.
Douglas Olson, PhD, a research scientist in the drug industry, first received the CLL diagnosis 16 years ago when he was 49 years old with a wife and four young children. At the time, there was no cure for CLL except bone marrow transplantation, which then had a survival rate of 50%. His life expectancy was 6 to 10 years without a transplant.
Over the next 13 years, Dr. Olson underwent several rounds of chemotherapy, each achieving a successively shorter remission, until the last treatment, when his CLL was found to be resistant. His oncologist, David Porter, MD, Professor of Medicine at the Hospital of the University of Pennsylvania, suggested a bone marrow transplant as his best hope for extending survival. But then Dr. Porter offered Dr. Olson enrollment in a phase I trial of the genetically engineered T-cell treatment.
“Both my wife and I are scientists. We believed this treatment could work. I entered the trial with no reservations. I trusted Dr. Porter, but most importantly, I saw this as an opportunity to advance the field,” he said.
The procedure to collect and infuse the T cells was relatively painless. Nothing happened for about 2 weeks after the procedure, and then Dr. Olson experienced severe flu-like symptoms, suggesting cytokine-release syndrome.
“I hoped this meant that the treatment was working,” he said. The symptoms persisted for more than a week, and then he was hospitalized for kidney problems, which ultimately resolved. Meanwhile, Dr. Porter gave him the news that the CAR-modified T cells were populating his bone marrow. “At that time, I became convinced that I would respond to the treatment,” Dr. Olson noted.
The following week, Dr. Olson was found to be in complete remission. “Dr. Porter told me, ’We can’t find a single cancer cell in your body. Your bone marrow is completely free of cancer cells.’”
“It has now been more than 2.5 years. I am still healthy and cancer-free. I ran my first half marathon a few months ago. I do require intravenous gamma globulin every 3 months to boost my immunity,” Dr. Olson said.
“I am just one life, but I am convinced that these scientists have found the key to saving my life and others,” he concluded.
Drs. June and Porter emphasize that the treatment is still in its early days and several challenges remain to be overcome. But, thus far, the experience in both children and adults has raised hopes that genetically engineered T cells will be an important breakthrough in the field of hematologic malignancy. ■
Disclosure: Dr. Porter has potential financial interest in CART19/CTL19 cells due to “upstream IP and patents” from licensure to Novartis. Conflict of interest is managed in accordance with University of Pennsylvania policy and oversight.
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