CAR-T vs. Cancer

At first, Tanis Milicevic’s local doctor told her to wait and see. Pregnant with her second child, Tanis had been sensitive about changes in her body when she felt a worrisome bump on the back of her head.

The doctor’s advice gave her temporary peace — the bump was small and she could just monitor it. Then, after her baby’s first birthday, Tanis felt a lump in her underarm.

“That’s when I knew that something was not right,” she says. Although she otherwise felt fine, her instincts about her health were correct. A biopsy showed she had non-Hodgkin’s lymphoma.

Tanis and her husband, Marko, learned that while her disease was slow growing at this stage, it would also be hard to cure. “It was a difficult pill to swallow, but we remained optimistic. You live life and push forward,” Marko says. They had to for their sons, 1-year-old Jonathon and 8-year-old Max.

Tanis, then 44, underwent radiation and then chemotherapy for two years. The treatments kept the cancer in remission for five years. It freed her to focus on her family and her business, a women’s contemporary fashion boutique.

When the cancer returned, Tanis came to Mayo Clinic.

Under the care of hematologist Han W. Tun, M.D., at Mayo’s campus in Florida, Tanis tried two new chemotherapy treatments to manage the recurrence, as well as a second relapse 18 months later. Her cancer was transforming and becoming more aggressive.

At the end of 2017, Tanis reviewed her options with Dr. Tun. It was just a matter of time before the next recurrence. The therapy for this type of cancer is usually a stem cell transplant, but Tanis had no suitable matching donor.

There was still hope. A new treatment was just approved by the Food and Drug Administration for Tanis’ type of lymphoma. Known as CAR-T cell therapy, it had been shown to improve remission and survival rates after other treatments had failed.

Mayo Clinic had taken part in pivotal clinical trials that led to FDA approval and was one of the first medical centers in the nation offering the therapy.

“I thought, I don’t think anything could come at a more perfect time for me,” she says. And in 2018, Tanis became the first patient at Mayo Clinic’s Florida campus to receive CAR-T cell therapy.

Revolutionary Treatment

CAR-T cell therapy, or chimeric antigen receptor-T cell therapy, is an individualized treatment that uses a patient’s own cells to fight cancer. T cells are a type of white blood cell in the immune system that protect people from infection. In CAR-T cell therapy, T cells are collected from a patient’s blood, genetically altered in a lab, multiplied and returned to the patient’s bloodstream. The alteration gives T cells the chimeric antigen receptor, which helps T cells recognize, latch onto and kill the intended cancer cells.

“I think that in the past 10 years or so, probably this is the most innovative and revolutionary treatment that our field has seen,” says hematologist and oncologist Mohamed A. Kharfan Dabaja, M.D., the director of the Blood and Marrow Transplantation Program and the Human Cellular Therapy Laboratory at Mayo Clinic’s Florida campus.

What has been exciting to cancer physicians and researchers is how CAR-T cell therapy is helping some patients achieve complete remission, even after other forms of treatments have failed. In complete remission, there are no symptoms or signs of cancer and it is not detectable, although it could return later.

“It has improved that complete remission rate by sevenfold,” Dr. Kharfan Dabaja says.

When patients achieve complete remission, they have a better chance of surviving, he says. Survival rates two years after treatment are shown to have improved — from as low as 15% to over 50% on CAR-T cell therapy, according to Dr. Kharfan Dabaja.

CAR-T cell therapy is fast acting, showing evidence of response within one to three months. It stands out among similar cancer therapies in terms of how it overcomes obstacles — such as vast numbers of cancer cells and suppression of the immune system by cancer — quickly and on its own.

Potential Options

The FDA has approved two CAR-T cell therapies. Presently, both can treat adults with certain types of non-Hodgkin’s lymphoma, but only one treats children and young adults, up to age 25, with B-cell acute lymphoblastic leukemia. The therapies are used after at least two previous treatment options have failed. They are not yet approved for use in earlier stages of the cancers.

Mayo Clinic is one of the few medical centers certified to offer the FDA-approved therapies. Mayo is also one of the few centers to have experience treating patients with the FDA-approved therapies and in clinical trials. The treatments are available at each of Mayo’s main campuses in Arizona, Florida and Minnesota.

CAR-T cell therapy requires the multidisciplinary specialty care that Mayo Clinic provides, especially once the CAR-T cells are infused back into a patient’s body, where they release chemicals as they kill cancer cells. The resulting symptoms can be severe.

“These are living drugs,” says Yi Lin, M.D., Ph.D. She leads the Cellular Therapeutics Cross-Disciplinary Group at Mayo Clinic Cancer Center. “Patients oftentimes need hospital, even ICU-level, support. They need to be at a very experienced center as they go through the treatment.”

Mayo Clinic continues to drive forward new research in CAR-T cell therapy, expanding clinical trials with a focus on using the treatment at earlier stages of cancer and in more types of cancer; countering the side effects and safely delivering treatment; and even using CAR-T cell therapy for conditions beyond cancer. All of Mayo’s main campuses will have trials open for various types of blood cancer this year.

Complete Remission

Tanis met with Dr. Kharfan Dabaja in 2018, and in late spring, she began the CAR-T cell treatment. Unfortunately, Tanis experienced severe side effects and was hospitalized longer than she expected, including time in the ICU.

While it was difficult for Tanis, Marko and their family, the outcome was the result they had hoped for: Six weeks after treatment, Tanis was in complete remission.

“This is a patient that had not seen a complete response for many, many years,” Dr. Kharfan Dabaja says. “Now she is experiencing a complete response, and with time, her condition has improved significantly, where she’s almost back to her normal life,” he says.

Tanis reached an important landmark when she was still in complete remission 90 days after her treatment. More than half the patients who reach the 90-day mark will be alive two years later, Dr. Kharfan Dabaja says.

Now, for the first time in a decade, Tanis and her family are thinking of a future without cancer.

“Tanis has gone through all the different treatments. This one definitely feels the most amazing,” Marko says. “It has allowed me to have my wife, and our kids to have their mom.”

“It’s given me the chance to live, and I’m forever grateful,” Tanis says, “My advice for anybody else who has lymphoma is to know that there is hope.”■

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