For Some, Cutting-Edge 'CAR-T' Treatment Unleashes 'Pac-Man' Cells Against Blood CancerPlay
Judith Wilkins, who has run a hair salon for 40 years, normally has too much energy to stay still. She’s always cutting or combing, blowing or fussing.
But by the summer of 2016, after 18 months of chemotherapy, Wilkins was exhausted, bald and running out of options.
Even so, when her doctor suggested she join a research trial testing an unproven therapy for her type of blood cancer, B-cell lymphoma, she wanted nothing to do with it.
"Trial? … No thank you," she told her doctor, Caron Jacobson, at the Dana-Farber Cancer Institute.
But Jacobson was persuasive.
“She looked right at me, and said, ‘Yeah, we are going to do this, and it’s going to be OK,’ ” recalls Wilkins, 59, who tends to tear up when she says Jacobson's name.
The type of treatment Wilkins got, called "CAR-T," uses the patient's own immune cells to fight cancer, and has shown remarkable results for certain blood cancers.
It 'Identifies The Bad B Cell And Eats It'
This week, the U.S. Food and Drug Administration approved the second therapy in this class, called Yescarta, to treat advanced B-cell lymphomas, like Wilkins’. The first CAR-T drug, Kymriah, received approval in August to treat an advanced form of childhood leukemia. There are nearly 200 clinical trials exploring CAR-Ts currently registered with the federal government.
Both therapies — and others like them still in the works — are tailored to each patient and re-engineer their body’s immune system to attack their cancer. The T in CAR-T refers to T cells, key soldiers of the immune system that normally attack invaders.
Eventually , CAR-T therapies are expected to help a large percentage of patients whose leukemia, lymphoma or multiple myeloma has resisted first-line treatments. Studies suggest that about 80 percent of Yescarta patients get some improvement from the treatment, with about 30 percent keeping those benefits long-term.
“I am the poster child for CAR-T cell therapy,” Wilkins said recently, while cutting and styling the silver hair of a longtime customer at her Scruples Hair Salon in Woburn. “It’s amazing what has happened with my body. ... It’s incredible, it really is.”
Jacobson had been working with Wilkins for two years to control her lymphoma, a type of cancer of the immune system's B cells, which normally make antibodies to keep infections under control. Repeated rounds of chemotherapy left Wilkins completely worn out, and wearing wigs like the ones she used to make for other women going through cancer treatment.
Three weeks after encouraging Wilkins to join the CAR-T study, the team at Dana-Farber drew her blood and sent it to a lab in California. There, technicians took out her T cells and re-engineered them to target a protein on her B cells, wiping out those cells. Even though some healthy B cells would likely be killed, too, adults can live without them or get intravenous immunoglobulin to help fight off infections.
Wilkins compares the CAR-T cells to the Pac-Man character from the old computer game: “The cell just cruises through your blood, identifies the bad B cell, and eats it.”
Glenn Dranoff, global head of immuno-oncology at the Novartis Institutes for Biomedical Research in Cambridge, has a more scientific explanation about what these re-engineered cells do next.
“They become part of the immune memory system, so they can persist for long periods of time and prevent a recurrence of the cancer,” Dranoff said.
On Aug. 1, 2016, Wilkins’ doctored T cells were infused back into her body.
Almost immediately, she felt terrible. Jacobson describes the typical reaction to CAR-T as “the flu on steroids.” Wilkins could barely move.
Luckily, she didn’t get the side effect she worried about most: the neurological problems that can leave patients confused and disoriented for days, though they almost always get back to normal within two weeks. Doctors are still learning how to manage the side effects of CAR-T, which are unlike those of other cancer therapies, Jacobson said.
Wilkins didn’t do much except sleep that August.
But a scan at the end of the month couldn’t find any cancer. By Labor Day, she’d started cutting hair again. And more than a year later, her scans are still clean.
Not For Everyone — And Not Cheap
CAR-T doesn’t help every cancer patient as much as it’s helped Wilkins — far from it.
For her type of cancer, about 30 percent get results like she did, with another 20 percent to 50 percent getting a shorter-term benefit.
But even for them, Jacobson said, the added time can mean attending a wedding, living to see a first grandchild or simply having enough time to come to terms with a very aggressive cancer and say goodbye. In some patients, B-cell lymphomas can take off very quickly after years of dormancy, and kill in a matter of weeks, she said.
According to studies, Kymriah, the Novartis therapy that won approval in late August, puts more than 80 percent of children with an advanced form of leukemia into remission, though some later relapse.
“The children who have this form of leukemia for which Kymria is approved previously had no meaningful options for achieving long-term survival despite many, many decades of research,” Dranoff said.
CAR-T therapies haven’t been around long enough to know if they are a permanent cure. But the first children to get the therapy are still going strong five years later.
Unfortunately, right now, the CAR-T approach only works against certain blood cancers, and most solid tumors don’t have an obvious target like B cells that people can live without. All over the world, researchers are trying to find targets that will allow them to kill tumor cells without also damaging crucial, healthy ones.
“The results in blood cancers have been pretty remarkable, but in solid tumors, it’s not clear that this therapy, the way it’s designed now, is going to be enough,” said Harvard Medical School assistant professor Marcela Maus, director of cellular immunotherapy at Massachusetts General Hospital.
T cells are great soldiers for fighting blood cancers because they naturally migrate to the bone marrow, where the blood cancers originate. It’s trickier to make sure they can get into a solid tumor, Maus said.
"The results in blood cancers have been pretty remarkable, but in solid tumors, it’s not clear that this therapy, the way it’s designed now, is going to be enough."Marcela Maus
In her own research, Maus is studying ways to get CAR-T approaches to work in patients with glioblastoma, the deadliest form of brain cancer -- and the type that Arizona U.S. Sen. John McCain is fighting now. It will take some time, she said, but she’s inspired by the relative speed with which CAR-Ts have been discovered and approved.
“It’s less than 10 years and we have something FDA-approved," she said. "If you think about the process of medicine, this has actually gone fairly quickly."
Another huge challenge with the CAR-T field is its cost. Kymriah is priced at $475,000 for the one-time treatment. Yescarta will cost $373,000. It’s not yet clear how the country will pick up this tab, or how these patients will afford co-pays -- some of which could cost as much as a house.
Both Mass. General and Dana-Farber will be among the first 16 sites nationwide to offer Yescarta. That means more patients will soon have access to the therapy, but now that it's FDA-approved and no longer experimental, they and their insurance companies will have to pay for it. Wilkins and others in the clinical trials had most of their costs covered by the drug companies.
Despite the challenges, Jacobson is optimistic about the future of CAR-T therapy to treat or even “cure” patients.
“As an oncologist, I never use the C word [for cure] even on my patients who are 10 to 15 years out from their therapies," she said. "But the durability of responses is very encouraging."
For her part, Wilkins, whose natural hair is now dyed a “mermaid green" setting off her bright blue eyes, said she’s eternally grateful for CAR-T — and her doctor, with whom she’s formed a close bond.
“Caron and I cry. Then we dance," she said, tearing up. "We dance, then we cry.”
This segment aired on October 23, 2017.