FDA Approves Axi-Cel for Large B-cell Lymphoma


The CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel; Yescarta) has been approved by the FDA for the treatment of adults with relapsed or refractory non-Hodgkin lymphoma (NHL), based on complete remission (CR) rate results from the phase II ZUMA-1 trial.

The FDA has approved axicabtagene ciloleucel (axi-cel; Yescarta) as a treatment for adult patients with relapsed or refractory large B-cell lymphoma, making the agent the second approved CAR T-cell therapies in the United States. The agent is indicated specifically following 2 prior therapies for those with diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma (TFL).

The approval was based on findings from the phase II ZUMA-1 trial, in which axi-cel demonstrated an objective response rate (ORR) of 72% and a complete remission (CR) rate of 51% (95% CI, 41%-62%). The median duration of response in those with a CR was not reached at the time of the assessment (95% CI, 8.1-not estimable).

“With CAR T therapy, we are reengineering a patient’s own immune system to detect and kill cancer cells, and the results have been impressive,” ZUMA-1 co-lead investigator Frederick L. Locke, MD, vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, said in a statement. “Many of the patients that received CAR T therapy had already relapsed several times with traditional treatments such as chemotherapy or hematopoietic stem cell transplant. Now, thanks to this new therapy many patients are in remission for months.”

In the ZUMA-1 trial, patients were enrolled into 2 cohorts consisting of those with DLBCL (n = 77) and those with PMBCL or TFL (n = 24). Prior to infusion of axi-cel, a conditioning regimen of fludarabine and cyclophosphamide was administered. Axi-cel was administered as a single infusion of modified autologous T cells at a target dose of 2 x 106CAR-positive T cells/kg.

All patients had chemorefractory disease and had received a median of 3 prior lines of therapy, with 54% refractory to 2 consecutive lines of therapy. Overall, 79% of patients were refractory to their last line of chemotherapy without having received prior autologous stem cell transplant (ASCT) while the remainder had relapsed within 12 months of ASCT.

In findings from the primary analysis presented at the 2017 AACR Annual Meeting, axi-cel demonstrated an ORR of 82% and a CR rate of 54%. After 8.7 months of follow-up, 39% of patients remained in CR. Those with DLBCL had an ORR of 82% and a CR rate of 49%. After 8.7 months of follow-up, the ORR in the DLBCL group was 36%, which included a CR rate of 31%. In the PMBCL/TFL group, the ORR was 83% and the CR rate was 71%. The 8.7-month ORR rate was 67%, with a CR rate of 63%.

Across all patients (N = 101), the median duration of response was 8.2 months. The median overall survival (OS) was not yet reached at the time of the analysis. The 6-month OS rate was 80%.

The most common grade ≥3 adverse events (AEs) were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%). Cytokine release syndrome occurred in 13% of patients and neurologic events were experienced by 28% of patients. To treat these events, 43% of patients received tocilizumab and 27% received corticosteroids.

The CAR T-cell therapy was approved with a boxed warning regarding CRS. To address the risk of CRS and neurologic toxicities, the FDA approved axi-cel with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). Additionally, certification and training will be required before hospitals will be cleared to administer the T cell therapy. The required training will focus on identifying and managing CRS and neurologic toxicity.

“Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer,” Scott Gottlieb, MD, FDA Commissioner, said in a statement. “This approval demonstrates the continued momentum of this promising new area of medicine and we’re committed to supporting and helping expedite the development of these products."


Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (Axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Presented at: 2017 AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract CT019.

Kite Pharma, which was recently acquired by Gilead, plans to market axi-cel at a list price of $373,000. The company plans to manufacture the treatment in El Segundo, California, which was the facility used for the ZUMA-1 trial, wherein cells were successfully manufactured 99% of the time and the median turnaround time was 17 days.

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