The Food and Drug Administration (FDA) has approved updated labeling for Yescarta® (axicabtagene ciloleucel) to include the use of prophylactic corticosteroids across all approved indications to help manage treatment-emergent adverse events, including cytokine release syndrome (CRS) and neurologic toxicities.

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy. It is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. It is also indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after 2 or more lines of systemic therapy.

The updated labeling is based on results of a new safety management cohort (Cohort 6) from the ZUMA-1 study (ClinicalTrials.gov Identifier: NCT02348216), which assessed the impact of prophylactic and earlier corticosteroids and/or tocilizumab and prophylactic levetiracetam on the incidence and severity of CRS or neurologic events. Cohort 6 included 39 adults who received dexamethasone 10mg orally once daily for 3 days, starting prior to Yescarta infusion. Cohorts 1 and 2 included 108 adults who received corticosteroids to manage CRS or neurologic events when they occurred.

Results showed that CRS events of grade 3 or greater occurred in 0% of patients in Cohort 6 and 13% of patients in Cohorts 1 and 2. At the time of data cut-off, 13% of patients in Cohort 6 reported a grade 3 or greater neurologic event, and 1 patient reported a late onset grade 5 event (following the data cut-off), compared with 31% of patients in Cohorts 1 and 2. In Cohort 6, the median time to onset for CRS was 5 days (range, 1 to 15 days) and the median time to onset of neurotoxicity was 6 days (range, 1 to 274 days).

Additionally, data published in the British Journal of Haematology showed that 68% of patients in Cohort 6 did not experience CRS or neurologic events within 72 hours of Yescarta infusion. One year follow-up of ZUMA-1 Cohort 6 also showed that the updated toxicity management strategy improved certain adverse events without compromising the activity of Yescarta.

“These new data will enable doctors to more easily and confidently manage treatment for patients,” said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development. “Since the first approval of Yescarta, Kite has worked closely with physicians to optimize all aspects of CAR T-cell therapy to enable as many patients as possible to have the chance to benefit from this treatment.” 

References

  1. US FDA approves new label update for CAR T-Cell therapy Yescarta® showing prophylactic steroid use improves management of cytokine release syndrome. News release. Kite Pharma, Inc. Accessed January 31, 2022. https://www.businesswire.com/news/home/20220131005477/en/U.S.-FDA-Approves-New-Label-Update-for-CAR-T-Cell-Therapy-Yescarta%C2%AE-Showing-Prophylactic-Steriod-Use-Improves-Management-of-Cytokine-Release-Syndrome
  2. Oluwole OO, Bouabdallah K, Munoz J, et al. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. Published online July 22, 2021. doi: 10.1111/bjh.17527
  3. Yescarta. Package insert. Kite Pharma, Inc.; 2021. Accessed January 31, 2022. https://www.gilead.com/-/media/files/pdfs/medicines/oncology/yescarta/yescarta-pi.pdf