Ten years ago, Stephan Grupp, MD, PhD, plunged into an unexplored area of pediatric cancer treatment with a 6-year-old patient for whom every treatment available for her acute lymphoblastic leukemia (ALL) had been exhausted.
Dr. Grupp, a pioneer in cellular immunotherapy at Children’s Hospital of Philadelphia, had just got the green light to launch the first phase 1 trial of chimeric antigen receptor (CAR) T-cell therapy for children.
“The trial opened at the absolute last possible moment that it could have been helpful to her,” he said in an interview. “There was nothing else to do to temporize her further. ... It had to open then or never.”
The patient was Emily Whitehead, who has since become a poster girl for the dramatic results that can be achieved with these novel therapies. After that one CAR T-cell treatment back in 2012, she has been free of her leukemia and has remained in remission for more than 10 years.
Dr. Grupp said that he is, at last, starting to use the “cure” word.
“I’m not just a doctor, I’m a scientist – and one case isn’t enough to have confidence about anything,” he said. “We wanted more patients to be out longer to be able to say that thing which we have for a long time called the ‘c word.’
“CAR T-cell therapy has now been given to hundreds of patients at CHOP, and – we are unique in this – we have a couple dozen patients who are 5, 6, 7, 9 years out or more without further therapy. That feels like a cure to me,” he commented.
First patient with ALL
Emily was the first patient with ALL to receive the novel treatment, and also the first child.
There was a precedent, however. After having been “stuck” for decades, the CAR T-cell field had recently made a breakthrough, thanks to research by Dr. Grupp’s colleague Carl June, MD, and associates at the University of Pennsylvania, Philadelphia. By tweaking two key steps in the genetic modification of T cells, Dr. June’s team had successfully treated three adults with chronic lymphocytic leukemia (CLL), two of whom were in complete remission.
But using the treatment for a child and for a different type of leukemia was a daunting prospect. Dr. Grupp said that he was candid with Emily’s parents, Tom and Kari Whitehead, emphasizing that there are no guarantees in cancer treatment, particularly in a phase 1 trial.
But the Whiteheads had no time to waste and nowhere else to turn. Her father, Tom, recalled saying: “This is something outside the box, this is going to give her a chance.”
Dr. Grupp, who described himself as being “on the cowboy end” of oncology care, was ready to take the plunge.
Little did any of them know that the treatment would make Emily even sicker than she already was, putting her in intensive care. But thanks to a combination of several lucky breaks and a lot of brain power, she would make a breathtakingly rapid recovery.
The ‘magic formula’
CAR T-cell therapy involves harvesting a patient’s T cells and modifying them in the lab with a chimeric antigen receptor to target CD19, a protein found on the surface of ALL cancer cells.