Prophylactic Corticosteroid Use Prior to Yescarta Infusion Reduces Incidence and Severity of Cytokine Release Syndrome and Neurologic Events in Relapsed/Refractory Large B-Cell Lymphoma

February 14, 2021 News /Bio ValleyBIOON/ -- Kite Pharma, the cell therapy subsidiary of Gilead Sciences, recently announced new analysis results from the ZUMA-1 trial evaluating Yescarta (axicabtagene ciloleucel), a CD19 CAR-T cell therapy, for adult patients with relapsed or refractory large B-cell lymphoma (LBCL) at the Transplantation and Cellular Therapy Meetings hosted by the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood and Marrow Transplant Research (CIBMTR).

In a new safety management cohort (Cohort 6) of the ZUMA-1 trial, the primary objective was to evaluate the impact of prophylactic corticosteroid use and early treatment with corticosteroids and/or tocilizumab on the incidence and severity of cytokine release syndrome (CRS) and neurologic events. In this cohort, patients with relapsed or refractory LBCL received oral dexamethasone 10 mg daily on the day of Yescarta infusion and for the subsequent two days.Compared with the ZUMA-1 pivotal cohorts (Cohorts 1 and 2), Cohort 6 initiated corticosteroids and tocilizumab earlier, demonstrating lower grades of CRS and neurologic events.. All 40 patients enrolled in Cohort 6 received at least one dose of corticosteroids.

In the preliminary analysis of Cohort 6, no cases of grade ≥3 cytokine release syndrome (CRS) were observed, and 13% of patients experienced grade ≥3 neurological events; no patients developed grade 5 neurological events by the data cutoff date. The median time to onset of CRS of any grade was 5 days, and the median time to onset of neurological events of any grade was 6 days. Sixty-eight percent of patients did not experience CRS or neurological events within 72 hours after Yescarta infusion. Ninety-five percent of patients in Cohort 6 demonstrated a therapeutic response to Yescarta, with 80% achieving complete response (CR); 63% of patients remained in response at the data cutoff date (median follow-up duration in the study was 8.9 months). The median duration of response (DOR) had not been reached.

Based on pre-specified prognostic factors for patients with LBCL, closely matched subgroups were selected from Cohort 6 and the pivotal cohort for a post hoc propensity score matching analysis. This analysis provided a more robust comparison of safety, efficacy, and pharmacokinetic/pharmacodynamic profiles between Cohort 6 and the pivotal cohort. In this propensity score-matched subset, the incidence of Grade ≥3 CRS in Cohort 6 (0%) was lower than that in matched patients from the pivotal cohort (13%), with a delayed median time to CRS onset (5 days vs. 2 days). Following propensity score matching, the severity and incidence of neurological events were generally similar between the cohorts. The propensity score matching analysis demonstrated that the response rate in Cohort 6 was comparable to that in the pivotal cohort.

Unlike conventional small-molecule or biologic therapies, CAR-T therapy is a living T-cell therapeutic product. The mechanism of Yescarta involves genetically modifying the patient’s T cells to express a chimeric antigen receptor (CAR) designed to target CD19, an antigen expressed on various hematologicTumorAntigenic proteins on the cell surface, including B-cell lymphoma andLeukemiaCells.

Yescarta was approved by the U.S.FDAApproved as the first CAR-T cell therapy for adult patients with relapsed or refractory large B-cell lymphoma (LBCL), with the specific indication for the treatment of adult patients with relapsed or refractory LBCL who have received two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBL), and DLBCL arising from follicular lymphoma (FL) (i.e., transformed FL, TFL). Yescarta is not indicated for the treatment of primary central nervous system lymphoma.

The US prescribing information for Yescarta includes a boxed warning regarding the risks of cytokine release syndrome (CRS) and neurotoxicity. The approval of Yescarta is also subject to a Risk Evaluation and Mitigation Strategy (REMS). Currently, the prophylactic use of corticosteroids in conjunction with Yescarta therapy has not been approved by any regulatory authority. Further clinical studies are required to evaluate the safety and efficacy of this prophylactic adverse event management strategy.

In China, Yescarta (axicabtagene ciloleucel injection [proposed], code FKC876) is being developed by Fosun Kite Biotechnology Co., Ltd. (FOSUN Kite), a joint venture established by Shanghai Fosun Pharmaceutical Group and Kite Pharma. In mid-March this year, Fosun Kite announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) had included the New Drug Application (NDA) for axicabtagene ciloleucel injection (proposed), a CAR-T cell therapy product, in the priority review program. The application is for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma.

Yikilirunsai Injection (code name FKC876) is a CD19-targeted autologous CAR-T cell therapy product, for which Fosun Kite has licensed the Yescarta (axicabtagene ciloleucel) technology from Kite Pharma and obtained authorization for localized production in China.

This product is the first CAR-T cell therapy product that Fosun Kite has advanced toward commercialization in China, and it is also the first CAR-T cell therapy product for which the National Medical Products Administration (NMPA) has formally accepted a marketing application. As a completely newTumorAs a treatment option, FKC876 can bring new hope and opportunities for patients in China with relapsed or refractory large B-cell lymphoma who have received two or more lines of systemic therapy. (Bioon.com)

Original Source: Kite Announces New ZUMA-1 Cohort Analysis Evaluating Prophylactic Corticosteroid Use With Yescarta in Patients With Relapsed or Refractory Large B-cell Lymphoma