A multi-center, single-arm, phase 2 trial of dasatinib in T follicular helper cell lymphomas
Abstract
T follicular helper cell lymphomas (TFHL) harbor activating T cell receptor (TCR) signaling mutations and epigenetic alterations, such as TET2 mutations. Here, we conduct a multi-center, single-arm, phase 2 trial of the tyrosine kinase inhibitor dasatinib in patients with relapsed/refractory TFHLs (jRCT2031190079). The primary outcome is the overall response rate (ORR) according to CT-based Lugano criteria 2014. Key secondary endpoints include ORR in RHOA-mutated patients and progression-free/overall survival. The main inclusion criteria consist of TFHL diagnosis and relapse following at least 1 prior chemotherapy regimen. Key exclusion criteria encompass central nervous system involvement, history of other malignancies, and receipt of chemotherapy or radiotherapy within 4 weeks. Nineteen patients are enrolled, with 18 receiving dasatinib and 17 evaluable for efficacy. Median age is 73 years, 50% are female, and angioimmunoblastic T cell lymphoma is the predominant subtype (n = 13). Dasatinib yields a 23.5% ORR, below the prespecified 30% endpoint. Treatment-related adverse events occur in 61.1% of patients (n = 11). Patients harboring TCR signaling mutations, especially those with RHOA p.G17V, achieve a 36.4% ORR, whereas no responses are observed in mutation-negative cases. Exploratory single-cell RNA sequencing reveals interferon-γ/tumor necrosis factor-enriched tumor microenvironments and peripheral expansion of cytotoxic T cell clones in responders. Conversely, early progression correlates with a high TET2 mutation burden in non-malignant immune cells, including CD8⁺ T cell subsets. While the primary outcome is below the prespecified endpoint, our exploratory findings implicate immune dysfunction involving TET2 mutations in limiting the therapeutic benefit of dasatinib.
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BibTeX
@article{suma2026multicenter,
title = {{A multi-center, single-arm, phase 2 trial of dasatinib in T follicular helper cell lymphomas}},
author = {Sakurako Suma and Mamiko Sakata-Yanagimoto and Yasuhito Suehara and Takahide Ara and Hideki Goto and Kensuke Usuki and Koji Izutsu and Motoko Yamaguchi and Noriko Fukuhara and Emiko Sakaida and Ken Ohmachi and Atsushi Uehara and Kosei Matsue and Satoshi Kimura and Hirokazu Nagai and Dai Maruyama and Mitsutaka Nishimoto and Kengo Takeuchi and Naoya Nakamura and Takashi Terauchi and Manabu Fujisawa and Yoshiaki Abe and Kenichi Makishima and Keiichiro Hattori and Tatsuhiro Sakamoto and Naoki Kurita and Hidekazu Nishikii and Futoshi Yoshino and Kenichi Yoshida and Yuko Hashimoto and Tomohiro Kaneta and Seishi Ogawa and Naoto Keino and Masahiko Gosho and Hiroyuki Hosokawa and Christian Steidl and Koichi Hashimoto and Shigeru Chiba},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78100-z},
url = {https://www.nature.com/articles/s41467-026-78100-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A multi-center, single-arm, phase 2 trial of dasatinib in T follicular helper cell lymphomas
AU - Sakurako Suma
AU - Mamiko Sakata-Yanagimoto
AU - Yasuhito Suehara
AU - Takahide Ara
AU - Hideki Goto
AU - Kensuke Usuki
AU - Koji Izutsu
AU - Motoko Yamaguchi
AU - Noriko Fukuhara
AU - Emiko Sakaida
AU - Ken Ohmachi
AU - Atsushi Uehara
AU - Kosei Matsue
AU - Satoshi Kimura
AU - Hirokazu Nagai
AU - Dai Maruyama
AU - Mitsutaka Nishimoto
AU - Kengo Takeuchi
AU - Naoya Nakamura
AU - Takashi Terauchi
AU - Manabu Fujisawa
AU - Yoshiaki Abe
AU - Kenichi Makishima
AU - Keiichiro Hattori
AU - Tatsuhiro Sakamoto
AU - Naoki Kurita
AU - Hidekazu Nishikii
AU - Futoshi Yoshino
AU - Kenichi Yoshida
AU - Yuko Hashimoto
AU - Tomohiro Kaneta
AU - Seishi Ogawa
AU - Naoto Keino
AU - Masahiko Gosho
AU - Hiroyuki Hosokawa
AU - Christian Steidl
AU - Koichi Hashimoto
AU - Shigeru Chiba
PY - 2026
DA - 2026/10/05
JO - Nature Communications
DO - 10.1038/s41467-026-78100-z
UR - https://www.nature.com/articles/s41467-026-78100-z
AB - T follicular helper cell lymphomas (TFHL) harbor activating T cell receptor (TCR) signaling mutations and epigenetic alterations, such as TET2 mutations. Here, we conduct a multi-center, single-arm, phase 2 trial of the tyrosine kinase inhibitor dasatinib in patients with relapsed/refractory TFHLs (jRCT2031190079). The primary outcome is the overall response rate (ORR) according to CT-based Lugano criteria 2014. Key secondary endpoints include ORR in RHOA-mutated patients and progression-free/overall survival. The main inclusion criteria consist of TFHL diagnosis and relapse following at least 1 prior chemotherapy regimen. Key exclusion criteria encompass central nervous system involvement, history of other malignancies, and receipt of chemotherapy or radiotherapy within 4 weeks. Nineteen patients are enrolled, with 18 receiving dasatinib and 17 evaluable for efficacy. Median age is 73 years, 50% are female, and angioimmunoblastic T cell lymphoma is the predominant subtype (n = 13). Dasatinib yields a 23.5% ORR, below the prespecified 30% endpoint. Treatment-related adverse events occur in 61.1% of patients (n = 11). Patients harboring TCR signaling mutations, especially those with RHOA p.G17V, achieve a 36.4% ORR, whereas no responses are observed in mutation-negative cases. Exploratory single-cell RNA sequencing reveals interferon-γ/tumor necrosis factor-enriched tumor microenvironments and peripheral expansion of cytotoxic T cell clones in responders. Conversely, early progression correlates with a high TET2 mutation burden in non-malignant immune cells, including CD8⁺ T cell subsets. While the primary outcome is below the prespecified endpoint, our exploratory findings implicate immune dysfunction involving TET2 mutations in limiting the therapeutic benefit of dasatinib.
SN - 2041-1723
ER -