The Amazing Transformation of CAR-T A Comic Book Introduction to CAR-T
By Larry Marion
Everything you’d ever want to know about chimeric antigen receptors for T cells (CAR-T) is in a nine-page article in the July 22, 2019 issue of The New Yorker magazine, and online as of July 19. “The Promise and Price of Cellular Therapies,” by Siddhartha Mukherjee, the Pulitzer Prize winning physician and author of the best-selling book “The Emperor of all Maladies,” explains how the revolutionary approach of using a patient’s modified T-cells to treat their cancer began more than 60 years ago in Seattle. More importantly, the article provides important insights into the high cost of providing CAR-T therapy and why that cost won’t decline rapidly any time soon.
The first two thirds of the article offer several important leukemia-related tidbits about the development of CAR-T therapy. The most important is that CAR-T success came almost as an accident—if a certain doctor didn’t have a daughter with an unrelated illness, we probably wouldn’t have CAR-T therapy today.
Dr. Carl June of the University of Pennsylvania in Philadelphia was treating a young girl, named Emily, with acute lymphoblastic leukemia (ALL) who had failed other treatments and wasn’t strong enough for a bone marrow transplant. Her doctors launched CAR-T therapy and she almost died from the cytokine explosion—in CAR-T therapy the T-cells destroy cancer cells so quickly and thoroughly that the resulting debris, called IL-6, can overwhelm a patient’s heart and other organs. However, Dr. June’s daughter who has juvenile arthritis, had just been treated with a new drug that blocks IL-6.
Here is how the article describes what happened next:
“As a last-ditch effort, [doctors] 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.”
“Days afterward, on her seventh birthday, she woke up. “Boom,” Dr. 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.”
And we all know what happened after the U of P reported on Dr. June’s success. Other medical institutions began or extended their own CAR-T research programs.
Indeed, the progress in CAR-T over the past seven years has been stunning. As noted in the article, “for a certain class of drug-resistant patients with CLL, the response rate with CAR-T therapy is around seventy-five per cent, to judge from the most recent trial data.”
Now the question is how society pays for CAR-T treatments, because they are expensive. The costs noted in the article will even stun CLL patients used to the $150,000 a year “list” price for ibrutinib or other novel agents:
- “A single dose of Kymriah, the Novartis developed CAR-T for pediatric ALL, is priced at $475,000″
- “Yescarta, a T-cell therapy designed for certain types of non-Hodgkin’s lymphoma, that number is $373,000″
- “These prices rival those of some of the most expensive procedures in American medicine. (A kidney transplant can be priced at $415,000, a lung transplant at about $860,000.)”
- “And these price tags don’t include the delivery of post-therapy care to CAR-T patients, who typically suffer complications from the infusion. Subsequent hospital stays and supportive care can drive the total costs to a million dollars or more.”
Why is the cost so high? Well, creating a CAR-T infusion is not like making a drug. “CAR-T still resembles a procedure, like a mastectomy or a liver transplant; it’s a matter of painstaking craft.
“The estimated cost to manufacture a typical CAR-T infusion is close to six figures. In short, even if CAR-T therapy were offered with no margin of profit, it would still rank with some of the most expensive procedures in medicine. Extracting cells from an individual patient, purifying them, genetically modifying them, and expanding their numbers into the millions will never be akin to churning out amoxicillin in a factory.”
The rest of the article talks about research to scale CAR-T so that it would cost less. Dr. Mukherjee also mentioned an anti-leukemia project he’s involved in that would protect the immune system from CAR-T.
It’s worth a read, though be sure you’re sitting in a comfortable chair.
Here is a link to the article:
https://www.newyorker.com/magazine/2019/07/22/the-promise-and-price-of-cellular-therapies
Larry Marion is the co-facilitator of the Boston chapter of the CLL Society and a former science, technology and business writer for what were once major magazines. He was diagnosed with CLL (11q, unmutated, complex karyotype) in 2005. Eleven cycles of chemo from 2010 to 2013, five years of ibrutinib and on Venetoclax since May. Despite all the progress of CAR-T, he’s hoping Venetoclax is the last anti-CLL drug he needs. “I’m a coward and hate pain and CAR-T looks painful.”
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