Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.

Abstract

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 106  CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

• Authors: Olalekan O Oluwole, Krimo Bouabdallah, Javier Muñoz, Sophie De Guibert, Julie M Vose, Nancy L Bartlett, Yi Lin, Abhinav Deol, Peter A McSweeney, Andre H Goy, Marie José Kersten, Caron A Jacobson, Umar Farooq, Monique C Minnema, Catherine Thieblemont, John M Timmerman, Patrick Stiff, Irit Avivi, Dimitrios Tzachanis, Jenny J Kim, Zahid Bashir, Jeff McLeroy, Yan Zheng, John M Rossi, Lisa Johnson, Lovely Goyal, Tom van Meerten
• Journal: British journal of haematology (Br J Haematol) Vol. 194 Issue 4 Pg. 690-700 (08 2021) ISSN: 1365-2141 [Electronic] England
• PMID: 34296427 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Kite, a Gilead Company. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Adrenal Cortex Hormones
• Antineoplastic Agents, Immunological
• Biological Products
• Dexamethasone
• axicabtagene ciloleucel

Topics

• Adrenal Cortex Hormones (adverse effects, therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Immunological (adverse effects, therapeutic use)
• Biological Products (adverse effects, therapeutic use)
• Cytokine Release Syndrome (drug therapy)
• Dexamethasone (adverse effects, therapeutic use)
• Female
• Humans
• Immunotherapy, Adoptive (adverse effects, methods)
• Lymphoma, Large B-Cell, Diffuse (therapy)
• Male
• Middle Aged