SOHO 最新进展更新与后续问题 | 超越罗米地辛：复发/难治性外周 T 细胞淋巴瘤的新治疗靶点与新兴策略

Peripheral T-cell lymphomas (PTCLs) represent heterogeneous aggressive non-Hodgkin lymphomas with dismal outcomes in the relapsed/refractory (R/R) setting. Following romidepsin's withdrawal from the R/R PTCL indication in 2021, the only FDA-approved agents are belinostat and pralatrexate, and Brentuximab Vedotin. Median overall survival following relapse is approximately 5. 8 months, highlighting the urgent need for effective therapies. Novel agents targeting distinct molecular pathways demonstrate promising activity. PI3K inhibitors, particularly duvelisib, achieved an ORR of 48% (complete response [CR] 33%) in the PRIMO trial. EZH2 inhibitors represent a mechanistically novel class: valemetostat produced an ORR of 43. 7% with a median duration of response of 11. 9 months. JAK/STAT inhibitors, including golidocitinib (ORR 44. 3%) and cerdulatinib (ORR 51. 9% in AITL/TFH), show subtype-selective activity.

Rational combinations yield superior efficacy: duvelisib plus romidepsin achieved ORR of 56% (CR 44%), while azacitidine combined with romidepsin produced ORR of 61% (CR 48%), particularly in TFH-phenotype disease (ORR 80%). DR-01, an anti-CD94 monoclonal antibody, represents a novel approach for cytotoxic T-cell lymphomas. A consistent pattern emerges: agents targeting epigenetic mechanisms demonstrate pronounced activity in nodal TFH lymphoma subtypes characterized by TET2, DNMT3A, and RHOA mutations.

The Ro-CHOP trial's failure in unselected populations, contrasted with efficacy signals in nTFHL subsets, underscores a critical lesson: PTCL is not one disease, and future trial designs must incorporate biomarker-driven enrichment strategies to advance precision therapeutics. Improved outcomes can be expected as we decipher more of the targetable dysfunctional molecular pathways in this group of lymphomas.