进行了一项 2 期国际、开放标签、非随机、单臂试验，以评估替比法尼（一种法尼基转移酶抑制剂）作为复发/难治性外周 T 细胞淋巴瘤 (PTCL) 单一疗法的有效性和安全性，并评估肿瘤突变谱作为反应的生物标志物。患有复发/难治性 PTCL 的成人接受替比法尼 300 mg 口服，每日两次，持续 21 天，周期为 28 天。主要终点是客观缓解率（ORR）；次要终点包括特定亚型的 ORR、无进展生存期 (PFS)、缓解持续时间 (DOR) 和不良事件 (AE)。纳入了 65 名 PTCL 患者：n=38 例血管免疫母细胞性 T 细胞淋巴瘤 (AITL)，n=25 例未另行指定的 PTCL (PTCL-NOS)，n=2 例其他 T 细胞淋巴瘤。所有患者的 ORR 为 39.7%（95% CI，28.1-52.5），AITL 的 ORR 为 56.3%（95% CI，39.3-71.8）。总体中位 PFS 为 3.5 个月（954% CI，2.1-4.4），AITL 为 3.6 个月（95% CI，1.9-8.3）。中位 DOR 为 3.7 个月（95% CI，2.0-15.3），AITL 患者的中位 DOR 最长（7.8 个月；95% CI，2.0-16.3）。中位总生存期为 32.8 个月（95% CI，14.4 至不适用）。替比法尼相关的血液学 AE 是可控的，包括：中性粒细胞减少症 (43.1%)、血小板减少症 (36.9%) 和贫血 (30.8%)；其他与替比法尼相关的 AE 包括恶心 (29.2%) 和腹泻 (27.7%)。发生一例与治疗相关的死亡。在 AITL 替比法尼应答组中，RhoA、DNMT3A 和 IDH2 突变的发生率分别为 60%、33% 和 27%，而在无应答组中，这一比例分别为 36%、9% 和 9%。 Tipifarnib 单药疗法在经过大量预处理的复发/难治性 PTCL（尤其是 AITL）中表现出令人鼓舞的临床活性，且安全性可控。 ClinicalTrials.gov NCT02464228.版权所有 © 2024 美国血液学会。

A phase 2, international, open-label, non-randomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary endpoint was objective response rate (ORR); secondary endpoints included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n=38 angioimmunoblastic T-cell lymphoma (AITL), n=25 PTCL not otherwise specified (PTCL-NOS), and n=2 other T-cell lymphomas. The ORR was 39.7% (95% CI, 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in AITL patients (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included: neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the non-responder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pre-treated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. ClinicalTrials.gov NCT02464228.Copyright © 2024 American Society of Hematology.