A life-saving cancer treatment out of reach for rural populations

Suzanne BeHanna initially turned down an experimental but potentially life-saving cancer treatment.

Three years ago BeHanna, then 62, newly married, was diagnosed with stage 4 lymphoma, sick from two failed chemotherapy cycles and sick of living in a trailer park near the University of Texas MD Anderson Cancer Center in Houston. It was the fall of 2019 and the treatment had forced her to migrate 750 miles east to rural New Mexico, where she had settled just months before her diagnosis.

Chimeric antigen receptor T-cell therapy might have been attractive to BeHanna if it had been available closer to home. But it is only offered in major transplant hospitals.

BeHanna had been living in Houston for six months, suffering from chemotherapy that made her feel bad and didn’t stop her cancer. She wanted to go home to die, but her husband wanted her to give CAR T-cell therapy a chance if her doctor approved.

The therapy uses the patient’s T cells, a key part of the immune system, to fight the cancer. Pioneering the therapy, Dr. Michel Sadelain, an immunologist at Memorial Sloan Kettering Cancer Center in New York, describes it as “a living drug – a T cell that has been weaponized against cancer”.

The treatment uses a process called apheresis to extract a patient’s T cells, then genetically alters the cells to add a receptor, the chimeric antigen, which binds to cancer cells.

When Suzanne BeHanna was diagnosed with stage 4 lymphoma, getting treatment meant living in Houston, near the University of Texas MD Anderson Cancer Center, 750 miles from her rural New Mexico home.Meredith Harbor

Manufacturing CAR T cells takes about 10 days, but because only three companies — Bristol Myers Squibb, Gilead Sciences and Novartis — have Food and Drug Administration approval to produce them commercially, receiving cells for infusion can take up to 10 days. a month. Once in a patient’s bloodstream, CAR T cells multiply, recognize cancer cells and kill them. If the therapy works, the patient’s cancer is usually in remission within a month.

Cost of using CAR T-cell therapy

For about 10 years, oncologists have been using CAR T-cell therapy in clinical trials for patients with blood cancers, including BeHanna, who has diffuse large B-cell lymphoma, and others with lymphoblastic leukemia. and multiple myeloma. But until recently, it was only FDA-approved for those who had already undergone two unsuccessful rounds of more conventional treatments, such as chemotherapy. For some types of blood cancer, therapy results in remission in more than half of patients. In April, for the first time, the FDA approved CAR T-cell therapy for lymphoma patients whose cancer has come back within 12 months after a single course of more conventional treatment.

That more people are eligible for CAR T-cell therapy seems like good news, but Dr. Jason Westin, an oncologist at MD Anderson, isn’t immediately optimistic. Westin, chair of the American Society of Clinical Oncology’s government relations committee, fears that as more patients become eligible, the cost — $375,000 to $475,000 — will strain the ability of insurers to support it.

Patients who meet the FDA’s threshold for treatment are a relatively small group. “If it’s a tiny, tiny fraction of patients who get expensive treatment, it’s hard on the system, but it might not be a stopping point,” Westin said. “But if you increase that slice of the pie for the patients who benefit from it, that starts to put more pressure on limited resources.”

Insurance companies, including Medicare, pay for CAR T-cell therapy, although according to the Leukemia & Lymphoma Society, they generally do not cover living expenses for patients who must live away from home, often for long periods of time. month. Blue Cross Blue Shield covered BeHanna’s medical expenses, but for living expenses, it only reimbursed her $5,000, a small fraction of what she and her husband spent living in Houston.

And new research into using the technology to treat other cancers, autoimmune diseases and even infections could put pressure on the already limited supply chain.

There are other, less expensive ways to make CAR T cells besides going to big pharma. Many researchers working on clinical trials, including Dr. Michael Chu of the Cross Cancer Institute in Edmonton, Alberta, use a bread machine-sized bioreactor made by Miltenyi Biotec to modify T cells in the lab. Some medical centers have established in-house T-cell manufacturing platforms that use other bioreactors and protocols.

But the FDA hasn’t granted medical centers and academic institutions permission to manufacture the cells commercially, and neither Sadelain nor Westin expect that to happen any time soon, if at all. .

Side effects of CAR T-cell therapy

Cost isn’t the only downside to CAR T-cell therapy. Side effects can be life-threatening — about 2% of patients die as a result of treatment, Chu said.

The most common side effect is a cytokine storm. Cytokines are small proteins that help direct the immune system, and their presence means the immune system is working. But sometimes the treatments send the immune system into overdrive, with results ranging from nausea and fever to organ failure.

The potentially toxic response dictated where the treatment can be administered. “If someone is having bad side effects, they need to be in a place that’s capable and set up to handle them,” Westin said. “A place used to giving treatment for breast cancer or lung cancer – they don’t know how to deal with what can potentially be a life-threatening side effect.”

Because of this, the treatment is only available at about 150 transplant centers, where specialists are available to oversee care, Westin said.

I could feel the tumor going away.

— Suzanne BeHanna

This creates an accessibility issue for about half of American adults who live at least half an hour from the nearest transplant center. “These patients have been through so much,” Chu said. “Asking them to go a bit further is going a bit too far in some cases, whether psychologically, financially or socially.”

This was the case for BeHanna. She did not want to participate in another clinical trial. But her husband, Chris, had done so much work, first to learn about treatment and then to lobby his doctor. “He promised me that if it didn’t work out I could go home, and that was all I cared about,” she said. “I didn’t expect it to work.”

To make sure her T cells were healthy enough to be genetically modified, BeHanna had to undergo more chemo, which meant more time in Houston. Approximately one month elapsed between apheresis and the time the CAR T cells were ready to be infused. “By the time I got my cells back, I was really, really sick, and I didn’t care if it worked or not,” she said.

For the first few days after the infusion, BeHanna felt fine. But on the third or fourth day, when she was asked a series of routine questions that tested her neurological function, she was clearly suffering from neurotoxicity – a side effect that reverses in most patients. His temperature rose. The cytokine storm had begun. She was transferred from CAR T-cell to the intensive care unit.

When she woke up a few days later, lucid but weak, all she remembered was that she had said “many mean and terrible things” to Chris.

BeHanna started crying as she described the first moments in the intensive care unit as she took her bearings and bent down to touch her belly. “It was clear to me for the first time in as long as I can remember that I could touch my belly and it wasn’t difficult,” she said. “I could feel the tumor going away.”

Before the treatment, which she underwent in October 2019, a CT scan showed tumors all over her body: in her armpits, chest, abdomen and groin. At the end of November, around Thanksgiving, BeHanna had another scan.

“I had no tumors,” she said. “It was surreal.”

BeHanna is grateful to be alive, but said she was frustrated that patients have to go through multiple rounds of harsh chemotherapy before they are allowed to undergo treatment that could so effectively eliminate their cancer.

“CAR-T is a bit difficult,” she said, but “it wasn’t difficult for me, because I don’t remember anything. It was something I was willing to risk, because either you do CAR-T or you go home and die.

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