Susanna Behana initially rejected an experimental but potentially life-saving cancer treatment.
Three years ago, the groom, then 62, was suffering from stage 4 lymphoma, sick from two failed rounds of chemotherapy and tired of living in a trailer park near the University of Texas MD Anderson Cancer Center in Houston. It was the fall of 2019, and treatment had forced her to migrate 750 miles east from rural New Mexico, where she had settled just months before her diagnosis.
Chimeric antigen receptor T-cell therapy might have appealed to BeHanna if it were available closer to home. But it’s only available at major transplant hospitals.
Behana had been living in Houston for six months, suffering from chemotherapy that made her feel terrible and did not stop her cancer. She wanted to go home to die, but her husband wanted her to CAR T-cell therapy a chance if her doctor approves it.
The therapy uses the patient’s T cells, a key part of the immune system, to fight the cancer. Dr. Michelle Sadeline, an immunologist at Memorial Sloan Kettering Cancer Center in New York and a pioneer in the therapy, describes it as “a living medicine — a T cell that’s armed against cancer.”
The treatment uses a process called apheresis to extract T cells from the patient and then genetically modify the cells to add a receptor, the chimeric antigen, that binds to cancer cells.
CAR T cells take about 10 days to make, but because only three companies — Bristol Myers Squibb, Gilead Sciences and Novartis — have FDA approval to make them commercially, getting the cells back for infusion can take up to a month. Once in the 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.
For about 10 years, oncologists have used 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 FDA-approved only for those who had already had two unsuccessful rounds of more conventional treatment, such as chemotherapy. In some types of blood cancer, therapy leads to remission more than half of the patients. In April, for the first time, the FDA approved CAR T-cell therapy for lymphoma patients whose cancer had relapsed within 12 months after just one round of more conventional treatment.
That more people will be eligible for CAR T-cell therapy seems like good news, but Dr. Jason Westin, an oncologist at MD Anderson, isn’t optimistic. Westin, chairman of the American Society of Clinical Oncology’s government relations committee, is concerned that as more patients become eligible, the cost — $375,000 to $475,000 — will strain insurers’ ability to support it.
Patients who meet the FDA threshold for treatment are a relatively small group. “If it’s a tiny, tiny fraction of patients who get expensive treatment, that’s hard on the system, but it might not be a breaking point,” Westin said. “But if you increase that piece of the pie for the patients who get that, it starts to put more stress on limited resources.”
Insurance companies, including Medicare, pay for CAR T-cell therapy, although the Leukemia & Lymphoma Society says they typically don’t cover living expenses for patients who must live away from home, often for months at a time. Blue Cross Blue Shield covered BeHanna’s medical expenses, but reimbursed her only $5,000 in child support, a fraction of what she and her husband spent to live in Houston.
And new research into using the technology to treat other cancers, autoimmune diseases and even infections could put pressure on an already limited supply chain.
There are other, cheaper ways to make CAR T cells than going to a big pharmaceutical company. Many researchers working on clinical trials, including Dr. Michael Chu of the Cross Cancer Institute in Edmonton, Alberta, use a bakery-sized bioreactor manufactured by Miltenyi Biotec to modify T cells in laboratories. Some medical centers have established their own T-cell production platforms that use other bioreactors and protocols.
But the FDA has not given approval to medical centers and academic institutions to produce the cells for commercial use, and neither Sadelain nor Westin expect that to happen soon, if at all.
Cost isn’t the only downside to CAR T-cell therapy. The Side Effects it can be life-threatening — about 2 percent of patients die as a result of the treatment, according to Chu.
The most common adverse reaction is a cytokine storm. Cytokines are small proteins that help target the immune system, and their presence means the immune system is working. But sometimes the treatment causes the immune system to go into overdrive, with results ranging from nausea and fever to organ failure.
The potentially toxic response to treatment determined where it could be administered. “If someone gets bad side effects, they need to be in a place that’s able and set up to manage them,” Westin said. “A place that’s used to giving treatment for breast cancer or lung cancer — they don’t experience how to manage what could potentially be a life-threatening side effect.”
For this reason, the treatment is only available in about 150 transplant centerswhere specialists are available to oversee care, Westin said.
This creates an accessibility problem for roughly half American adults who live at least half an hour from the nearest transplant center. “These patients have been through so much,” Chu said. “To ask them to go a little further is in some cases too far, be it on the psychological, financial or social front.”
Such was the case with BeHanna. She did not want to participate in another clinical trial. But her husband, Chris, had done so much work, first learning about the treatment and then lobbying her doctor. “He promised me if it didn’t work I could go home and that was all I cared about,” she said. “I didn’t expect it to work.”
To ensure her T cells were healthy enough to be genetically modified, Behana had to have more chemotherapy, which meant more time in Houston. About a month passed between the apheresis and when the CAR T cells were ready for infusion. “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, BeHannah felt fine. But on the third or fourth day, when she was asked a routine series of questions that tested her neurological function, she was apparently experiencing neurotoxicity, a side effect that is reversible in most patients. Her temperature rose. The cytokine storm had begun. She was transferred from the CAR T-cell unit to the intensive care unit.
When she woke up a few days later, conscious but weak, all she could remember was saying “very mean, horrible things” to Chris.
Behana began to cry as she described the first moments in the intensive care unit, when she found her bearings and reached over to touch her stomach. “For the first time in as long as I can remember, I realized I could touch my belly and it wasn’t hard,” she said. “I could feel the tumor disappearing.”
Before the treatment she had in October 2019, a scan showed tumors all over her body: in her armpits, breasts, abdomen and groin. In late November, around Thanksgiving, BeHanna had another scan.
“I had no tumors,” she said. “It was surreal.”
Behana is grateful to be alive, but said she is disappointed that patients are required to undergo multiple rounds of heavy chemotherapy before being allowed to continue with a treatment that can so effectively eliminate their cancer.
“CAR-T is a little rough,” she said, but “it wasn’t hard for me because I don’t remember anything about it. It was something I was willing to risk because you either do CAR-T or you go home and die.
Photo: marekuliasz, Getty Images
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism on health issues. Along with policy analysis and polling, KHN is one of three major operational programs in the KFF (Kaiser Family Foundation). KFF is a charitable, non-profit organization providing information on health issues to the nation.