Parents of British 4-year-old seek T-cell leukemia therapy in Philadelphia

Last month, the national health-care system in England announced a deal with Novartis to make its expensive T-cell therapy Kymriah available to children with leukemia who have exhausted standard treatment options.

Yet, the parents of 4-year-old Zac Oliver are desperately trying to raise more than $600,000 so they can leave England by next month and get Kymriah at Children's Hospital of Philadelphia, where it was pioneered in collaboration with the University of Pennsylvania.

English authorities say costly Kymriah is for use by children who relapse after conventional treatment stops working. That's the same as the approved U.S. protocol. But Zac's parents believe relapse would be a death sentence, because he has an ultra-rare, ultra-aggressive subtype of acute lymphoblastic leukemia (ALL) with an especially dismal prognosis. He is expected to relapse soon, because the chemotherapies he has been on since his diagnosis in May have not eradicated the blood cancer.

"When it comes back, it usually ends in a rapid death," his mother, Hannah Oliver-Willets, an occupational therapist, said from Broseley, a small town northwest of Manchester.

Zac's case illustrates the wrenching dilemmas shaping the real-world rollout of Kymriah and a competitor, Kite Pharma's Yescarta. These personalized, genetically engineered "CAR T-cell" therapies pose unprecedented challenges in terms of cost, production, toxicities, and access — as well as uncertainties about the value of using them earlier in the disease course.

All of which helps to explain why CHOP continues to study the drug and draw patients worldwide, despite Kymriah's approval last year in the United States and this year by the European Commission. Ten percent of kids treated with the T-cell therapy at CHOP come from other countries.

"We get all these emails from parents across the world," CHOP oncologist Stephan Grupp, who led the pivotal clinical trial of Kymriah, said early this year. "We're trying to look at access. We're really interested in figuring out how to help patients who won't have access in their own countries, at least not for years."

About 6,000 youngsters are diagnosed with ALL each year in the U.S. and Europe, and standard treatments — chemo, radiation and stem-cell transplants — cure 85 percent of them.

But the outlook is grim for those who repeatedly relapse. And for the tiny fraction like Zac, who have ALL with chromosome alterations called near haploid or hypodiploid, treatment itself is often deadly, because it goes on for so long and does so much damage.

"We will not watch him die. We will not wait for his little body to become weak from all the toxic chemotherapy before giving our little boy what could be a lifesaving treatment," Zac's father, Mark Garbett, a heating and plumbing contractor, wrote on the JustGiving website.

CHOP would not discuss Zac's case, or confirm the plan to treat him. But in an email, a spokesperson said CHOP has successfully used Kymriah to fight Zac's type of ALL:  "We have treated patients with rare, very high-risk ALL subtypes, including hypodiploid. We haven't yet published results from individual subtypes because the numbers are so small, but what we see broadly across these unfavorable subtypes is similar responses compared to ALL in general."

For ALL in general, T-cell therapy has shown stunning effectiveness. In the global clinical trial of 95 youngsters that led to Kymriah's approval in the U.S., 80 percent went into remission, and more than 40 percent were alive a year later. The first child ever treated, Emily Whitehead, 13, of Philipsburg, Pa., remains cancer-free six years after her Lazarus-like rescue.

Still, almost all children who receive the new therapy suffer serious or even life-threatening complications, a result of immune system overstimulation. The necessary intensive hospital care can inflate the cost of treatment with Kymriah — priced at $475,000 in the U.S. — to more than $1 million. (The negotiated price of Kymriah in England has not been disclosed.)

Oliver-Willets said CHOP has agreed to cover the T-cell therapy and all medical care for $604,000. Family and friends have raised about half of that.

Ideally, she said, Zac would get to CHOP by November, before he has time for a full-blown relapse,  and begin the long, complicated treatment process. It would involve harvesting his disease-fighting T cells, genetically programming them to attack the leukemia cells, multiplying the T cells for about three weeks, then reinfusing them.

Zac also would be enrolled in a CHOP study intended to reduce the toxicity of overstimulating the immune system, she said.

While the ability to dramatically boost the immune response is a breakthrough, the response is so abrupt that at worst, it can send the body into shock and organ failure. Emily Whitehead almost died of the terrifying syndrome but was saved by the speculative use of a then-new rheumatoid arthritis drug that blunted the immune overreaction.

The new study aims to optimize the timing of the arthritis drug by giving it earlier to children with lots of cancer in their blood, because a high tumor burden is believed to increase the risk of the syndrome.

The syndrome "could be worse for Zac if he has lots of cancer," his mother said.

In all, Zac's treatment and recovery in Philadelphia would take about four months. Oliver-Willets said the logistics and implications of uprooting the family, including Zac's stepfather and little brother, are still being worked out.

"But we are going to try to get Zac into that tiny percentage that survive and are cured," she said.