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TFH phenotype and response to tucidinostat in relapsed/refractory PTCL: analysis of patients from a phase IIb trial
Koji Izutsu1, Ayumi Fujimoto2,3, Shinya Rai4
1Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. kizutsu@ncc.go.jp.
Abstract:
T follicular helper (TFH)-derived peripheral T-cell lymphomas (PTCLs) harbor frequent mutations in epigenetic regulators and are sensitive to epigenetic therapies. The histone deacetylase inhibitor tucidinostat demonstrated efficacy in relapsed/refractory PTCL, especially angioimmunoblastic T-cell lymphoma (AITL), in a phase IIb trial; however, the lack of TFH phenotyping has prevented assessment of the predictive value of this phenotype across a broader PTCL spectrum. Therefore, we retrospectively analyzed patients originally diagnosed with AITL or PTCL not otherwise specified (NOS) based on 2008 World Health Organization criteria who participated in the aforementioned trial. TFH phenotype was defined as the expression of ≥ 2 TFH markers. Among the 23 evaluable patients, the TFH group (n = 17) included six with AITL and 11 with PTCL-NOS exhibiting TFH features, and the non-TFH group included six patients with PTCL-NOS. The objective response rate was numerically higher in the TFH group (12/17, 70.6%) than in the non-TFH group (2/6, 33.3%; P = 0.162). Three patients with the TFH phenotype maintained a progression-free survival exceeding 3 years. These findings highlight the potential long-term benefit of tucidinostat in patients with TFH-derived PTCL, supporting the distinct susceptibility of this subtype to epigenetic modulation.
Insights
T follicular helper (TFH)-derived lymphomas show promise with epigenetic therapy. Tucidinostat demonstrated potential long-term benefits in patients with TFH-phenotype peripheral T-cell lymphomas (PTCLs), suggesting this subtype is susceptible to epigenetic modulation.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- T-cell lymphomas (PTCLs) often have mutations in epigenetic regulators.
- Epigenetic therapies show promise for PTCL treatment.
- Tucidinostat, a histone deacetylase inhibitor, demonstrated efficacy in a phase IIb trial for relapsed/refractory PTCL, particularly angioimmunoblastic T-cell lymphoma (AITL).
Purpose of the Study:
- To retrospectively analyze the predictive value of T follicular helper (TFH) phenotype in patients with AITL or PTCL not otherwise specified (NOS) treated with tucidinostat.
- To assess the efficacy of tucidinostat in PTCL patients based on TFH phenotype.
Main Methods:
- Retrospective analysis of patients diagnosed with AITL or PTCL-NOS (2008 WHO criteria) from a phase IIb tucidinostat trial.
- TFH phenotype defined by expression of ≥2 TFH markers.
- Comparison of objective response rate (ORR) and progression-free survival (PFS) between TFH and non-TFH groups.
Main Results:
- Of 23 evaluable patients, 17 had a TFH phenotype (including AITL and PTCL-NOS) and 6 had a non-TFH phenotype (PTCL-NOS).
- The ORR was numerically higher in the TFH group (70.6%) compared to the non-TFH group (33.3%; P=0.162).
- Three TFH-phenotype patients achieved PFS >3 years, indicating potential long-term benefit.
Conclusions:
- The TFH phenotype may predict a favorable response to tucidinostat in PTCL.
- TFH-derived PTCL exhibits distinct susceptibility to epigenetic modulation.
- Tucidinostat holds potential for long-term benefit in patients with TFH-derived PTCL.
