The FDA approved the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, making it the second such treatment for blood cancers in the United States. The therapy is indicated for adults with certain non-Hodgkin lymphomas who have tried at least two other treatments.

The FDA approved the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Yescarta; Kite Pharma) in late October, the second such treatment for blood cancers in the United States.

Axicabtagene ciloleucel is indicated for the treatment of adults with certain non-Hodgkin lymphomas, including diffuse large B-cell lymphoma, the most common form. Patients must have relapsed after, or not responded to, at least two other treatments before receiving axicabtagene ciloleucel. Treatment involves collecting and genetically modifying a patient's T cells to express CARs so that they bind to and destroy CD19-expressing cancer cells and normal B cells.

The safety and efficacy of axicabtagene ciloleucel were established in a multicenter clinical trial of more than 100 adults with refractory or relapsed large B-cell lymphomas. The complete remission rate was 51%.

The first FDA-approved CAR T-cell therapy, tisagenlecleucel (Kymriah; Novartis), was approved in August. The two therapies work in much the same way, but they have different indications, with tisagenlecleucel approved to treat only acute lymphoblastic leukemia in patients age 25 or younger.

“These approvals represent a very important development in modern cancer treatment,” says Steven Rosenberg, MD, PhD, chief of the Surgery Branch at the NCI. “These treatments are very effective in patients with lymphomas and leukemias,” he notes, adding that the first case study of CAR T-cell therapy was published in 2010, and that that patient remains cancer-free. Rosenberg led the team that originally developed the therapy.

Axicabtagene ciloleucel carries boxed warnings for two potentially fatal side effects: neurologic toxicity and cytokine release syndrome (CRS), a flu-like systemic response to the proliferation of CAR T cells. In the phase II ZUMA-1 trial, CRS occurred in 94% of patients; 13% of patients experienced symptoms that required aggressive treatment or were considered life-threatening.

For this reason, axicabtagene ciloleucel's use requires a risk evaluation and mitigation strategy. Sites administering the treatment must obtain special certification, including training on recognizing and managing side effects. Currently, 16 facilities are certified to dispense axicabtagene ciloleucel. Kite hopes to increase that number to 70 within the next 12 months.

The list price of axicabtagene ciloleucel is $373,000. However, the personalized nature of the treatment, the extensive monitoring program, and the relatively high response rate may justify the expense. “The best way to save clinical care dollars is to cure people rather than moving them from one ineffective treatment to another,” says Rosenberg. –Jordan Calmes-Miller

For more news on cancer research, visit Cancer Discovery online at