Pulitzer Prize-winning author Siddhartha Mukherjee’s article in the New Yorker provides a fascinating and easy to read history of CAR-T therapy and the incredible story of Emily Whitehead, the first paediatric patient to be treated (and cured) with CAR-T for her refractory acute lymphoblastic leukaemia. Emily recently celebrated the milestone of being 7 years cancer-free.
“We thought she was going to die,” June recalled. “I wrote an e-mail to the provost at the university, telling him the first child with the treatment was about to die. I feared the trial was finished. I stored the e-mail in my out-box, but never pressed send.”
Doctors at chop and at Penn worked overnight to determine the cause of the fever. Once again, they found no evidence of infection; instead, they found elevated blood levels of cytokines. In particular, levels of a cytokine known as IL-6 were nearly a thousand times higher than normal. Ludwig had barely survived his cytokine storm; Emily’s was a full-on hurricane.
By a strange twist of fate, June’s own daughter had a form of juvenile arthritis, and so he knew about a drug for the condition—approved only recently by the F.D.A.—that blocks IL-6. As a last-ditch effort, Grupp rushed a request to the hospital pharmacy, asking for the off-label use of the new drug. The medication was supplied, and a nurse injected Emily with a dose in the picu.
Days afterward, on her seventh birthday, she woke up. “Boom,” June said, waving his hands in the air. “Boom,” he repeated. “It just melted away. We did a bone-marrow biopsy twenty-three days later, and she was in a complete remission.”
“I have never seen a patient that sick get better so quickly,” Grupp told me.
The deft management of what has come to be known as cytokine-release syndrome—and Emily’s startling recovery—probably saved the field of CAR-T therapy, and helped energize cell therapy in general. She remains in deep remission to this day. No cancer is detectable in her marrow or in her blood.
“If Emily had died,” June told me, “it’s likely that the whole trial would have been shut down,” and perhaps not just at chop. (Other hospitals were offering experimental CAR-T therapy, too.) He wonders whether, without her recovery, there would be any living drugs.