Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma

ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for sec...

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Vydané v:Blood advances Ročník 4; číslo 19; s. 4898 - 4911
Hlavní autori: Locke, Frederick L., Rossi, John M., Neelapu, Sattva S., Jacobson, Caron A., Miklos, David B., Ghobadi, Armin, Oluwole, Olalekan O., Reagan, Patrick M., Lekakis, Lazaros J., Lin, Yi, Sherman, Marika, Better, Marc, Go, William Y., Wiezorek, Jeffrey S., Xue, Allen, Bot, Adrian
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Elsevier Inc 13.10.2020
American Society of Hematology
Predmet:
Antigens, CD19 - therapeutic use
Humans
Immunobiology and Immunotherapy
Immunotherapy, Adoptive
Inflammation
Tumor Burden
ISSN:2473-9529, 2473-9537, 2473-9537
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Shrnutí:ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for secondary end point analysis were not clearly predictive of efficacy; these included Eastern Cooperative Oncology Group performance status (0 vs 1), age, disease subtype, disease stage, and International Prognostic Index score. We interrogated covariates included in the statistical analysis plan and an extensive panel of biomarkers according to an expanded translational biomarker plan. Univariable and multivariable analyses indicated that rapid CAR T-cell expansion commensurate with pretreatment tumor burden (influenced by product T-cell fitness), the number of CD8 and CCR7+CD45RA+ T cells infused, and host systemic inflammation, were the most significant determining factors for durable response. Key parameters differentially associated with clinical efficacy and toxicities, with both theoretical and practical implications for optimizing CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02348216. •Axi-cel durable responses were associated with low baseline tumor burden, low systemic inflammation, and high product CCR7+CD45RA+ T cells.•Distinct sets of factors associated with durable response, grade ≥3 cytokine release syndrome, and grade ≥3 neurologic events. [Display omitted]
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2473-9529
2473-9537
2473-9537
DOI:10.1182/bloodadvances.2020002394