Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma.

Autor: Locke FL; Moffitt Cancer Center, Tampa, Florida. Electronic address: frederick.locke@moffitt.org., Neelapu SS; M.D. Anderson Cancer Center, Houston, Texas., Bartlett NL; Washington University School of Medicine, St. Louis, Missouri., Lekakis LJ; University of Miami Health System, Sylvester Comprehensive Cancer Center, Miami, Florida., Jacobson CA; Dana-Farber Cancer Institute, Boston, Massachusetts., Braunschweig I; Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York., Oluwole OO; Vanderbilt-Ingram Cancer Center, Nashville, Tennessee., Siddiqi T; City of Hope National Medical Center, Duarte, California., Lin Y; Mayo Clinic, Rochester, Minnesota., Timmerman JM; UCLA David Geffen School of Medicine, Los Angeles, California., Kersten MJ; Amsterdam UMC, University of Amsterdam, Amsterdam, Cancer Center Amsterdam, Netherlands, on behalf of HOVON/LLPC., Zheng Y; Kite, a Gilead Company, Santa Monica, California., Zhang T; Kite, a Gilead Company, Santa Monica, California., Nater J; Kite, a Gilead Company, Santa Monica, California., Shen R; Kite, a Gilead Company, Santa Monica, California., Miao H; Kite, a Gilead Company, Santa Monica, California., Kim JJ; Kite, a Gilead Company, Santa Monica, California., Miklos DB; Stanford University School of Medicine, Stanford, California.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2024 Aug 24. Date of Electronic Publication: 2024 Aug 24.
DOI: 10.1016/j.jtct.2024.08.018
Abstrakt: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Most patients treated with axi-cel experience cytokine release syndrome (CRS) and/or adverse neurologic events (NEs). To explore potential approaches for reducing CAR T-cell-related toxicities with axi-cel, several safety expansion cohorts were added to the pivotal ZUMA-1 trial. ZUMA-1 Cohort 3 was an exploratory safety cohort that investigated the use of the IL-6 receptor blocking antibody tocilizumab and anticonvulsant levetiracetam as prophylaxis against CRS and NEs in patients treated with axi-cel. Patients with R/R LBCL were enrolled in Cohort 3 and received conditioning chemotherapy on d- 5 through -3 followed by a single infusion of axi-cel (2 × 10 6 cells/kg) on d 0. Prophylactic tocilizumab (8 mg/kg) was administered 48 h after axi-cel infusion. Primary endpoints were incidence and severity of CRS and NEs. Key secondary endpoints included the incidence of adverse events, objective response rate (ORR), duration of response, progression-free survival, overall survival (OS), and biomarker analyses (eg, circulating CAR T cells, cytokines, chemokines). Forty-two patients were enrolled in Cohort 3, 38 of whom received axi-cel. In the 24-month analysis, any-grade CRS and NEs occurred in 92% and 87% of patients, and Grade ≥3 CRS and NEs occurred in 3% and 42% of patients, respectively. One Grade 5 NE (cerebral edema) occurred. With 24-mo minimum follow-up, the ORR was 63%, and 39.5% of patients had ongoing response. With 48-month follow-up, median OS was 34.8 mo (95% CI, 5.4-not estimable). CAR T-cell expansion in ZUMA-1 Cohort 3 was comparable with pivotal Cohorts 1 and 2. Consistent with tocilizumab-mediated inhibition of IL-6R, serum IL-6 levels were increased relative to Cohorts 1 and 2. Grade ≥3 NEs were associated with elevated IL-6 levels, proinflammatory cytokines, and myeloid cells in the cerebrospinal fluid. Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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