Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma.

Autor:	Witzig T; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN., Sokol L; Department of Hematology and Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL., Kim WS; Division of Hematology-Oncology, Sungkyunkwan University School of Medicine Samsung Medical Center, Seoul, South Korea., de la Cruz Vicente F; Department of Hematology, Hospital Universitario Virgen del Rocío, Sevilla, Spain., Martín García-Sancho A; Hematology Department, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación Biomédica en Red - Cáncer (CIBERONC), Salamanca, Spain., Advani R; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA., Roncero Vidal JM; Servei Hematologia ICO Girona, Hospital Universitari de Girona Dr Josep Trueta, Catalunya, Spain., de Oña Navarrete R; Hematology Department, MD Anderson Cancer Center, Madrid, Spain., Marín-Niebla A; Department of Hematology, Vall D'Hebron Institute of Oncology, Hospital Universitario Vall d'Hebron, Barcelona, Spain., Rodriguez Izquierdo A; Servicio de Hematología y Hemoterapia, Hospital Universitario 12 de Octubre, Madrid, Spain., Terol MJ; Hospital Clínico Universitario de Valencia, Valencia, Spain., Domingo-Domenech E; Hematology Department, Institut Català d'Oncologia, Hospital Duran i Reynals, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain., Saunders A; Kura Oncology Inc, Boston, MA., Bendris N; Kura Oncology Inc, Boston, MA., Mackey J; Kura Oncology Inc, Boston, MA., Leoni M; Kura Oncology Inc, Boston, MA., Foss F; Division of Hematology, Yale University School of Medicine, New Haven, CT.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Sep 10; Vol. 8 (17), pp. 4581-4592.
DOI:	10.1182/bloodadvances.2024012806
Abstrakt:	Abstract: A phase 2, international, open-label, nonrandomized, 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 end point was objective response rate (ORR); secondary end points 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, and n = 2 other T-cell lymphomas. The ORR was 39.7% (95% confidence interval [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 patients with AITL (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 nonresponder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pretreated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. This trial was registered at www.ClinicalTrials.gov as #NCT02464228. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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