A phase 2 study of axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma in Japan: 1-year follow-up and biomarker analysis

Koji Kato, Nobuharu Fujii, Shinichi Makita, Hideki Goto, Junya Kanda, Kazuyuki Shimada, Koichi Akashi, Koji Izutsu, Takanori Teshima, Natsuko Fukuda, Tokuhito Sumitani, Shota Nakamura, Hiroyuki Sumi, Shinji Shimizu, Yasuyuki Kakurai, Kenji Yoshikawa, Kensei Tobinai, Noriko Usui, Kiyohiko Hatake

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Axicabtagene ciloleucel (axi-cel) is an autologous, CD19-targeting chimeric antigen receptor T‑cell therapy. We recently reported the 3-month follow-up results of a phase 2, multicenter, open‑label, single-arm study of axi-cel in Japanese patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) (JapicCTI-183914). Here, we present 1-year efficacy and safety data and biomarker analysis data regarding mechanisms of resistance to axi-cel. Primary and secondary endpoints included investigator-assessed objective response rate (ORR), serious adverse events, and treatment-emergent adverse events. Axi-cel pharmacokinetics were also examined. Biomarker analysis was performed by cytokine measurement, immunohistochemistry, RNA sequencing, and whole-exome sequencing. At a median follow-up of 13.4 months, ORR was 86.7% (13/15 patients), and the complete response (CR) rate improved to 53.3% (8/15 patients) due to response conversion. Seven patients experienced disease progression, and one achieved CR after re-treatment with axi-cel. No new safety concerns were detected. Plausible resistance mechanisms to axi-cel varied among patients but included CD19 downregulation, programmed death-ligand 1 upregulation, and increased macrophage and angiogenesis signatures. The 1-year efficacy and safety of axi-cel were confirmed in Japanese patients with R/R LBCL. Resistance to treatment may involve multiple factors, including target antigen loss and an unfavorable tumor environment. Clinical trial registration: Japan Clinical Trials Information; JapicCTI-183914.

本文言語英語
ページ(範囲)409-420
ページ数12
ジャーナルInternational journal of hematology
117
3
DOI
出版ステータス出版済み - 3月 2023

!!!All Science Journal Classification (ASJC) codes

  • 血液学

フィンガープリント

「A phase 2 study of axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma in Japan: 1-year follow-up and biomarker analysis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル