A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas.

Autor:	Moskowitz AJ; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical Center, New York, NY., Ghione P; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.; Lymphoma Service, Roswell Park Comprehensive Cancer Center, Buffalo, NY., Jacobsen E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Ruan J; Lymphoma Service, Weill Cornell Medical Center, New York, NY., Schatz JH; Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL; and., Noor S; Dermatology Service., Myskowski P; Dermatology Service., Vardhana S; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical Center, New York, NY., Ganesan N; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Hancock H; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Davey T; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Perez L; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Ryu S; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Santarosa A; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Dowd J; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Obadi O; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Pomerantz L; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Yi N; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Sohail S; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Galasso N; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Neuman R; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Liotta B; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Blouin W; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY., Baik J; Department of Pathology., Geyer MB; Leukemia Service., Noy A; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical Center, New York, NY., Straus D; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical Center, New York, NY., Kumar P; Department of Pathology., Dogan A; Department of Pathology., Hollmann T; Department of Pathology., Drill E; Department of Biostatistics., Rademaker J; Department of Radiology, and., Schoder H; Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY., Inghirami G; Lymphoma Service, Weill Cornell Medical Center, New York, NY., Weinstock DM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Horwitz SM; Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY.; Department of Medicine, Weill Cornell Medical Center, New York, NY.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2021 Dec 30; Vol. 138 (26), pp. 2828-2837.
DOI:	10.1182/blood.2021013379
Abstrakt:	Signaling through JAK1 and/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1/2 inhibitor ruxolitinib for patients with relapsed/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7). Patients enrolled onto 1 of 3 biomarker-defined cohorts: (1) activating JAK and/or STAT mutations, (2) ≥30% pSTAT3 expression among tumor cells by immunohistochemistry, or (3) neither or insufficient tissue to assess. Patients received ruxolitinib 20 mg PO twice daily until progression and were assessed for response after cycles 2 and 5 and every 3 cycles thereafter. The primary endpoint was clinical benefit rate (CBR), defined as the combination of complete response, partial response (PR), and stable disease lasting at least 6 months. Only 1 of 7 patients with MF had CBR (ongoing PR > 18 months). CBR among the PTCL cases (n = 45) in cohorts 1, 2, and 3 were 53%, 45%, and 13% (cohorts 1 & 2 vs 3, P = .02), respectively. Eight patients had CBR > 12 months (5 ongoing), including 4 of 5 patients with T-cell large granular lymphocytic leukemia. In an exploratory analysis using multiplex immunofluorescence, expression of phosphorylated S6, a marker of PI3 kinase or mitogen-activated protein kinase activation, in <25% of tumor cells was associated with response to ruxolitinib (P = .05). Our findings indicate that ruxolitinib is active across various PTCL subtypes and support a precision therapy approach to JAK/STAT inhibition in patients with PTCL. This trial was registered at www.clincialtrials.gov as #NCT02974647. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
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