FDA Approves Immunotherapy That’s Less Intensive for People With Lymphoma

A man and a woman sit on a boat wearing life jackets and holding a large icicle. An iceberg sticking out of the water is behind them.

An immunotherapy clinical trial brought Joe Crimi’s lymphoma under control and allowed him to get back to his normal life quickly. He’s shown here traveling in Iceland with his wife, Debbie.

When Joe Crimi found out that his lymphoma had returned after he’d been in remission for almost a year, he was “pretty depressed,” he remembers. His doctor at the hospital on Long Island where he’d received his initial treatment told him he would probably need a bone marrow transplant (BMT) and referred him to Memorial Sloan Kettering Cancer Center (MSK).

“I’d read up on bone marrow transplants, and I knew how tough they are on your body,” says Joe, now 67 and a retired high school teacher, basketball coach, and summer camp director. “I figured I’d be in treatment for about a year.”

But the first time he met with MSK hematologic oncologist Parastoo Dahi, Joe learned he might be eligible for a clinical trial testing a different type of treatment. “I could tell right away that Dr. Dahi was a supersmart person, and I felt so much better after talking to her,” he says.

Last month, the U.S. Food and Drug Administration (FDA) approved the treatment Joe received for his cancer — diffuse large B cell lymphoma (DLBCL), a type of non-Hodgkin lymphoma. It’s the most common type of lymphoma and diagnosed in about 25,000 people in the United States every year.

The Opportunity To Take a ‘Living Drug’

Joe enrolled in a clinical trial that compared BMT, a standard treatment, with a therapy often referred to as a “living drug” because it only needs to be given once to continue fighting cancer. This drug — axicabtagene ciloleucel (Yescarta®) — is a form of immunotherapy known as chimeric antigen receptor (CAR) T therapy.

In the trial, immune cells called T cells were removed from Joe’s bloodstream and sent to a lab, where they were engineered to contain a gene that enabled them to recognize and destroy his cancer. In June 2019, just a few days before his 65th birthday, Joe’s cells were infused back into his body.

The therapy was successful for Joe and others in this trial, called ZUMA-7. Researchers found that the average time that patients remained free of disease was two and a half times longer with CAR T therapy. After 24 months, 41% of patients in the axicabtagene ciloleucel group had no disease recurrence, compared with 16% in the BMT group.

Based on those results, the FDA approved axicabtagene ciloleucel for patients with DLBCL whose disease does not respond to the initial treatment or who have relapsed less than a year after another treatment. The drug was previously approved for treating people with DLBCL who did not respond to two or more previous treatments.

What is CAR T?
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“The ZUMA-7 trial was one of several trials looking at CAR T therapy compared to BMT in these patients. Two of the trials, including ZUMA-7, have suggested that this form of treatment may be better than BMT for many patients with DLBCL,” says MSK medical oncologist Miguel-Angel Perales, Chief of the Adult Bone Marrow Transplant Service. “One of the things we’re doing now is comparing ZUMA-7 to trials that looked at other CAR T therapies, in order to determine the strengths and weaknesses of each of them. This will also help us improve the treatments for our patients.”

Challenging Side Effects

Although his CAR T treatment was ultimately successful, Joe faced challenges along the way. “About a week after I got my cells put back, the side effects really hit me. I was basically incoherent,” he says. “My wife laughs about it now, but when they asked me what the date was, I would say it was November 75th, 2089. I was so confused, and it was really kind of scary.”

This side effect, called neurotoxicity, is relatively common in people who receive CAR T therapy and can occur days or weeks after patients receive their infusion. In the ZUMA-7 trial, 21% of patients had it. The underlying causes of neurotoxicity in people receiving these treatments are not fully understood, but experts believe they are caused by inflammatory proteins called cytokines crossing the blood-brain barrier.

“Neurotoxicity can cause confusion, tremors, difficulty with communication, behavioral changes, seizure, or, rarely, swelling of the brain,” Dr. Dahi says. “The treatment for this condition is supportive and consists primarily of steroids and anti-seizure therapy. In the majority of cases, these neurologic side effects are short-lived and reversible with appropriate management.”

Clinical trials are an essential part of our quest to find better ways to prevent, treat, and cure cancer. Almost every cancer treatment patients receive today is the result of a clinical trial.

During his time in the trial and afterward, Joe felt a tremendous level of support from his entire care team, especially physician assistant (PA) Theresa Elko, who was the Clinical Research PA for the ZUMA-7 trial. Elko provided much of Joe’s medical care in collaboration with Dr. Dahi, assisting with the monitoring of his side effects and response to treatment and making sure that the care he received was consistent with the clinical trial protocol.

A Chance To Travel and Coach Again

Thankfully, Joe’s neurotoxicity lasted only about a week. As soon as he started feeling better, he was anxious to get home. In August 2019, he was discharged from the hospital, first to the MSK Residence on East 75th Street and later to his house in Queens. By October, he was able to go back to his basketball coaching job. “I had already retired from teaching, and this was going to be my last year coaching. I didn’t want to miss it,” he says. “If I’d had the BMT instead, I wouldn’t have been able to go back to work that soon.”

Joe got his wish. His team made it to the championship game in February 2020. They lost, but he was grateful to be able to see them through their season.

Although the COVID-19 pandemic has slowed them down a bit, Joe and his wife, Debbie, have been able to travel. Since he’s recovered from cancer treatment, they’ve been to Arizona, Croatia, Iceland, and Turks and Caicos. He has regular checkups and scans with Dr. Dahi. He has shown no signs of his cancer coming back.

“I feel very fortunate that I was able to get into this trial,” Joe says. “It changed my life.”

The ZUMA-7 trial was supported by Kite Pharmaceuticals, a Gilead company.

Dr. Dahi has relationships with or financial interests in Kite Pharmaceuticals, OncLive, and Targeted Oncology. Dr. Perales has relationships with or financial interests in Cidara Therapeutics Inc., Incyte, Karyopharm, Merck & Co. Inc., Miltenyi Biotec Incorporated, MorphoSys AG, NexImmune, Novartis, and Omeros.