KYMRIAH (Tisagenlecleucel)

KYMRIAH®, also called tisagenlecleucel, is a one-time individualized treatment for certain leukemias and lymphomas. It may be a good option if a cancer has returned or when at least two other treatments have failed. The U.S. Food and Drug Administration (FDA) has approved KYMRIAH® for:

• Children and youth up to 25 years old with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)
• Adults 18 and older with relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

KYMRIAH® is what’s known as a CAR-T cell therapy, the first to be approved by the FDA. It is a form of gene therapy that modifies people’s own T cells — critical white blood cells in the immune system — enhancing their ability to detect and destroy cancerous cells.

Once treated in the lab, the T cells produce structures called chimeric antigen receptors (CARs) on their surface. These enable the T cells to zero in on specific proteins on the surface of B cells (including cancerous B cells), latch onto the cells, and destroy them. CAR-T cells treated with KYMRIAH® also contain costimulatory proteins, which make them even better at attacking cancer cells.

Learn about CAR-T cell therapy.

KYMRIAH® is a multi-step procedure that takes about six weeks from start to finish.

• T cell collection: The first step is T cell collection, which involves placing a large catheter into a person’s vein for blood collection. A machine separates out the T cells, a process called leukapheresis, and gives the rest of the blood back. Leukapheresis takes three to six hours and will require an overnight stay at Boston Children’s. If too few T cells are collected, the process is repeated the next day to get more.
• T cell treatment: The cells are next sent to Dana Farber’s Cell Manipulation Facility, where they’re frozen and packaged and sent to Novartis, KYMRIAH’s manufacturer. Novartis then treats the cells with gene therapy, a process that takes an estimated 24 to 28 days.
• Conditioning chemotherapy: If testing shows that you or your child are ready for treatment, the next step is chemotherapy conditioning. This five-day process kills any remaining circulating T cells to make room for the new, treated cells and requires a stay in our Bone Marrow Transplant Unit.
• KYMRIAH® infusion and post-treatment follow-up: KYMRIAH® is then infused through an intravenous line, a process that takes about a half hour. Your care team will then keep you or your child under close observation for at least one month. We ask that you stay near the hospital during this time so we can intervene quickly should serious side effects develop. Thereafter, we will schedule follow-up visits.

• B-cell ALL: The FDA approved KYMRIAH® based on a clinical trial called ELIANA. In early results, 82 percent of patients with relapsed or refractory pediatric precursor B-cell ALL had their cancer go into remission after a single dose of KYMRIAH. They remained cancer free for 1.2 to 14 months or more after treatment.
  More recent data published in The New England Journal of Medicine found that 76 percent of those receiving KYMRIAH® were still living one year later, and that 50 percent were alive with no return of the cancer. The latest results from KYMRIAH’s manufacturer (not yet published at this writing) indicate that 55 percent of those treated were still alive after more than five years.
• Large-cell lymphoma: In another study published in The New England Journal of Medicine, 40 percent of adults with diffuse large B-cell lymphoma had complete responses to KYMRIAH, and 12 percent had partial responses. One year later, overall relapse-free survival estimated to be 65 percent.

KYMRIAH® is a very powerful medicine. It is available only at specific treatment centers such as ours that have a Risk Evaluation and Mitigation Strategy in place. After a KYMRIAH® infusion, you or your child will remain in the hospital (or stay close by) until the risk for serious side effects wanes. In some cases, admission to the intensive care unit (ICU) is necessary.

In the study that led to FDA approval of KYMRIAH® for B-cell ALL, 84 percent of patients had severe or life-threatening adverse reactions. More recent data put that at 73 percent. In a study of patients with diffuse large B-cell lymphoma, 63 percent had severe or life-threatening adverse events believed to be caused by KYMRIAH.

The most common and dangerous side effect is cytokine release syndrome (CRS) — a strong, exaggerated immune reaction to the CAR-T cell therapy that causes inflammatory molecules (cytokines) to be rapidly released into the bloodstream. Also known as a “cytokine storm,” CRS can develop anywhere from several days to several weeks after the infusion. It can be effectively treated with a monoclonal antibody called tocilizumab (ACTEMRA), which the FDA approved together with KYMRIAH.

Other common side effects include:

• Hypogammaglobulinemia (low antibody levels), leading to an increased risk of infections
• Toxicity to the nervous system, including altered consciousness, confusion, agitation, seizures, balance problems, and difficulty speaking or understanding. This has been reported in 40 percent of patients.
• Decreased appetite, headache, a racing heart, nausea, diarrhea, vomiting, fatigue
• Low blood pressure
• Bleeding episodes
• Poor blood oxygenation
• Acute kidney injury

The extent to which insurance providers will cover KYMRIAH® varies. We encourage you to talk with your health insurance company and medical team. Boston Children’s Financial Services staff will guide you through the insurance approval process.