Diffuse large B-cell lymphoma
The US Food and Drug Administration (FDA) has approved axicabtagene ciloleucel (Yescarta™, formerly KTE-C19) for use in adults with relapsed or refractory large B-cell lymphoma who have received 2 or more lines of systemic therapy.
Axicabtagene ciloleucel is the first chimeric antigen receptor (CAR) T-cell therapy approved to treat lymphomas.
The approval encompasses diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and transformed follicular lymphoma.
Axicabtagene ciloleucel is not approved to treat primary central nervous system lymphoma.
The FDA’s approval of axicabtagene ciloleucel was based on results from the phase 2 ZUMA-1 trial. Updated results from this trial were presented at the AACR Annual Meeting 2017.
Risks
Axicabtagene ciloleucel has a Boxed Warning in its product label noting that the therapy can cause cytokine release syndrome (CRS) and neurologic toxicities. Full prescribing information for axicabtagene ciloleucel is available at https://www.yescarta.com/.
Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel was approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use. The FDA is requiring that hospitals and clinics that dispense axicabtagene ciloleucel be specially certified.
As part of that certification, staff who prescribe, dispense, or administer axicabtagene ciloleucel are required to be trained to recognize and manage CRS and nervous system toxicities. In addition, patients must be informed of the potential serious side effects associated with axicabtagene ciloleucel and of the importance of promptly returning to the treatment site if side effects develop.
Additional information about the REMS program can be found at https://www.yescartarems.com/.
To further evaluate the long-term safety of axicabtagene ciloleucel, the FDA is requiring the manufacturer—Kite, a Gilead company—to conduct a post-marketing observational study of patients treated with axicabtagene ciloleucel.
Access and cost
The list price of axicabtagene ciloleucel is $373,000.
The product will be manufactured in Kite’s commercial manufacturing facility in El Segundo, California.
In 2017, Kite established a multi-disciplinary field team focused on providing education and logistics training for medical centers. Now, this team has provided final site certification to 16 centers, enabling them to make axicabtagene ciloleucel available to appropriate patients.
Kite is working to train staff at more than 30 additional centers, with an eventual target of 70 to 90 centers across the US. The latest information on authorized centers is available at https://www.yescarta.com/authorized-treatment-centers/.
