Treating the untreatable: David’s story

Three years ago, a routine blood test showed that David B. Duggan, MD, had a high white-blood-cell count, suggesting an infection or illness of some sort. 

“But I felt great,” recalled Duggan, a hematologist in New York. In his late 60s at the time, Duggan was active — he cycled, swam and worked on his 185-year-old farmhouse. He also taught medical students, conducted research and treated patients with leukemia, lymphoma and other blood cancers at the State University of New York Upstate Medical University in Syracuse, N.Y. 

But within days of the blood test, Duggan received grim news. He had leukemia — specifically, T-cell prolymphocytic leukemia, or T-PLL, a rare, aggressive and often fatal cancer.

“Ironically, as a hematologist, I was quite familiar with T-PLL,” Duggan said. “I’ve treated patients with it, and it can progress quickly. Standard treatments aren’t terribly satisfying.” So, he started getting his affairs in order. He and his wife of 39 years, Lynn, took a two-week bucket-list trip to Ireland with family. He looked forward to being a part of major family events, including the birth of his first grandson, Colin, and the marriage of his youngest child. He stopped accepting new patients.  

My job was to be there for my patients.
I wasn’t sure if I’d be around.

But then, Duggan discovered a phase 1 clinical trial 885 miles from home at Siteman Cancer Center. The international, multicenter trial is evaluating an innovative cellular immunotherapy that was developed by WashU Medicine’s John F. DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor of Medicine, and his colleagues, fellow physician-scientists Geoffrey L. Uy, MD, co-leader of the Hematopoietic Development and Malignancy Program at Siteman and a professor of medicine in the oncology division; Michael Kramer, MD, PhD, WashU Medicine instructor in medicine; and Armin Ghobadi, MD, clinical director of the Center for Gene and Cellular Therapy and a professor of medicine in the oncology division at WashU Medicine.

The clinical trial is partly funded by Wugen, a startup cofounded by DiPersio, who also directs WashU Medicine’s Center for Gene and Cellular Immunotherapy at Siteman. The company — which is developing several lines of cell-based immunotherapies for various cancers — was cofounded by WashU Medicine physician-scientist Todd Fehniger, MD, PhD, co-leader of the Hematopoietic Development and Malignancy Program at Siteman and a professor of medicine in the division of oncology; Matthew Cooper, PhD, a former faculty member and Wugen’s chief scientific officer; and Melissa Berrien-Elliott, PhD, a former postdoc in Fehniger’s lab. 

The trial involves CAR T-cell therapy, a type of cellular immunotherapy that uses genetically modified T cells to attack cancer cells. This particular CAR T-cell therapy is unique in that it is genetically engineered to attack T cell cancers, such as Duggan’s, rather than B cell cancers, the typical target of CAR T-cell therapies. But using genetically modified T cells to kill and eliminate the cancerous T cells is tricky, because the modified T cells risk mistaking themselves for the cancer and succumbing to friendly fire rather than eliminating the leukemia.

A second genetic modification helps overcome this challenge by eliminating the T cells’ ability to target one another, which also stops the cells from attacking the body’s healthy tissues, preventing a life-threatening side effect of treatment called graft-versus-host disease. These modifications further allow the therapeutic T cells to be collected from any healthy donor without concern about finding someone with an immune system match, which can take time and delay treatment against an aggressive disease.  

Using the novel CAR T-cell therapy, Ghobadi administered the infusion to Duggan in early 2024. “He had a beautiful expansion of CAR T cells circulating throughout his body,” Ghobadi said. “It eventually led to the elimination of his malignant T cells, basically ridding the body of leukemia.”

In addition to Duggan, other patients who have received the CAR T-cell therapy have gone into remission, Ghobadi said. “The trial has introduced a new and exciting opportunity for treating patients who otherwise lacked other options.”

“As a doctor, I understand death,” Duggan said. “After my diagnosis, I was afraid I had little time left. But Siteman has given me access to WashU Medicine oncologists who are international leaders in their fields as well as this innovative clinical trial that’s granted me time. I am grateful because, boy, I sure enjoy living.”