Kaitlyn Johnson, a seven-year-old from outside Dallas who loves cheerleading, her science classes, and the color pink, and Justin Pritikin, a 17-year-old high school senior in New Jersey looking forward to starting college, have never met. But they’ve got one important thing in common: they were both among the courageous participants in clinical trials of a completely new way to treat cancer.

The medicine is called Kymriah, and is among a new wave of therapies that use a patient’s own cells as medicine. It was approved by the Food and Drug Administration on Aug. 30 and heralded as a historic event in the annals of cancer treatment.

Kaitlyn and Justin’s are both stories of hope. But they also illustrate the early nature of understanding of this new technology, and of how society will pay for it.

The technology is CAR-T, for chimeric antigen-receptor T-cell therapy. It uses viruses to deliver genetic material to patients’ immune cells, equipping them with homing devices to track down markers on cancer cells.

“That is, in this way, a living therapy,” said Dr. Jay Bradner, president of the Novartis Institutes for BioMedical Research. Novartis markets Kymriah. “This growth of T-cells in the patient will allow these serial killers to take out millions of cancer cells.”

The FDA cleared the medicine to treat patients up to 25 years old with acute lymphoblastic leukemia for whom other therapies have stopped working. It’s a small number of patients, about 600 a year in the U.S., but a group with few other options.

The agency called the approval a “historic action… ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.”

Earlier that same week, biotechnology giant Gilead spent $11.9 billion to acquire Novartis’s CAR-T competitor, Kite Pharma. Shares of Juno Therapeutics, third in line with CAR-T therapies in development, soared. CAR-T is the new darling of the drug industry.

It’s a moment years in the making. Years that Kaitlyn and Justin contributed to. But here is where their stories diverge.

For Kaitlyn, the journey to CAR-T started in late 2011. She was just 18 months old when her parents, James and Mandy, noticed she had strange bruises. Then a fever. A bewildering trip to the hospital revealed the worst.

“I don’t even remember the doctor’s name,” Mandy recalled last week. “I was like, ‘So, does my daughter have cancer?’ And she was like ‘Has nobody told you yet? Yes, she does.'”

Then started the two and a half years of punishing chemotherapy that’s standard of care for acute lymphoblastic leukemia, the most common form of childhood cancer. For more than 80 percent of kids, that regimen — though grueling to get through — works.

Kaitlyn was among the unlucky few for whom it didn’t. Just a few months after she finished treatment, the cancer came back.

“I said, so whatever she wants to do this weekend, we’re gonna do it,” Mandy said. “Because she’s not going to be able to go back outside. She’s not going to be able to play with her friends.”
James said, “We were going to return back to our old normal.”

But another month of chemotherapy failed Kaitlyn too. It was then that her doctor suggested they try something very few people had: CAR-T, still in clinical trials. They were nervous, but, fueled by the hope of success stories before them, they said yes.

“We were ready to throw that Hail Mary pass for treatment,” James said. “We had no other options.”

Just weeks after Kaitlyn received her modified T-cells, James and Mandy got a late-night call from Kaitlyn’s doctor. They assumed it was bad news. But it was just the opposite.

“She says there’s no detectable signs of cancer,” James said. “And I think we just cried, you know? … Within six months, our pendulum had swung from, ‘We’re going to lose our child, potentially,’ to: ‘We beat cancer.'”

Three years later, Kaitlyn is still cancer free. For James and Mandy, seeing Kymriah approved was a joyful moment.

It was “very breathtaking for me,” Mandy said. “You know, just thinking, ‘Wow, we are a part of this, you know: to help hundreds, thousands of other kids.’ And I’m always thinking, ‘I almost chose not to do this.'”

Fifteen hundred miles away, in New Egypt, New Jersey, Justin Pritikin was going through the same thing. For him, the journey to CAR-T started when he was 12.

The years of chemotherapy — an extra year for boys, said his mother, Jill — gave him 14 months free from cancer and toxic treatment before it failed him, too.

Justin enrolled in a clinical trial whose goal was to assess ways to tamp down a common, and potentially severe, side effect of CAR-T. Called cytokine release syndrome, it can result from overactivation of the immune system.

It’s an “on-target risk,” explained Dr. Gwen Nichols, chief medical officer of the Leukemia & Lymphoma Society, which supports research into CAR-T. “Any time you activate the immune system, you activate a lot of chemicals in the body that help chew up the targets.”

Cytokine release syndrome can lead to high fevers and organ damage, and can be life-threatening at its most serious. But researchers have found ways to control it using anti-inflammatory drugs, such as those used for rheumatoid arthritis.

Justin, though, didn’t experience those side effects, Jill said.

“Just a little elevated temperature,” she recalled in an interview this week.

A month later, a check on Justin’s bone marrow revealed the therapeutic T-cells were still active, and there were no B-cells, the target of the treatment.

“This whole time he feels amazing, it was like he was back to normal,” Jill said. “After years of chemotherapy, it was nice to see.”

But his three-month checkup wasn’t as positive. The T-cells were nowhere in sight. And B-cells had started to return.

It wasn’t a relapse; the B-cells weren’t leukemic, Jill said. But it appeared the CAR-T treatment had stopped working.

The outcomes for Kaitlyn and Justin are part of the mysteries of medicine: why a cutting-edge therapy works for years for one person, and just months for another.

When Kymriah was approved, Novartis announced a pricing model for patients covered by government insurers to account for those for whom the medicine doesn’t work.

“The CAR-T therapy is administered to all patients who need it,” Novartis’s Bradner explained. “If the medicine is working at a fixed period of time, then Novartis is compensated. And if it doesn’t, then we feel good at having provided this chance for that patient.”

If Kymriah is controlling patients’ cancer after a month, its price tag is $475,000.

The cost “definitively shattered oncology drug pricing norms,” Memorial Sloan-Kettering Cancer Center’s Dr. Peter Bach, Dr. Sergio Giralt, and Dr. Leonard Saltz wrote in an editorial in the Journal of the American Medical Association last week.

They point out, though, Kymriah’s impressive response rate of 80 percent, with 25 percent of patients seeing their cancer recur within 6 months, and one-year survival of 80 percent.

“Alternative treatments do not achieve these types of results,” they wrote.

Still, had Justin been among patients acccessing the drug through a government program, rather than in a clinical trial, his insurance would be on the hook for $475,000, even though the therapy appeared to stop working three months in.

“While this is a welcome innovation in reimbursement, Novartis under this arrangement would still be expected to be paid for 83% of cases (if clinical experience parallels the trial),” the Memorial Sloan-Kettering doctors wrote. “Alternative strategies could be used.”

Jill Pritikan, though, says she still considers Justin’s CAR-T therapy a success. Before he entered the trial, he wasn’t well enough to attempt a stem cell transplant, another last-resort option for patients with ALL. The CAR-T helped him get well enough to try.

“The T-cells, in our minds, did exactly what we needed them to: got him into strong remission without chemotherapy. And still today he’s technically in remission,” Jill said. “That’s kind of the best way to go into transplant anyway.”

Justin was preparing to receive his stem cell transplant on Thursday.

It’s still early days for understanding CAR-T, said the Leukemia & Lymphoma Society’s Dr. Nichols.

“This is the tip of the iceberg,” she said. “This is just the beginning of a whole new era of thinking in the science of how we treat cancer.”

Analysts at Cowen Research estimate the market for CAR-T therapies could reach $5 billion to $10 billion annually at its peak — if drug companies and researchers are successful in extending it to additional forms of cancer and more patients who, like Kaitlyn and Justin, run out of options among existing medicines.

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