Paul M Barr1, Hongli Li2, Catherine Spier2, Daruka Mahadevan2, Michael LeBlanc2, Mansoor Ul Haq2, Bryan D Huber2, Christopher R Flowers2, Nina D Wagner-Johnston2, Steven M Horwitz2, Richard I Fisher2, Bruce D Cheson2, Sonali M Smith2, Brad S Kahl2, Nancy L Bartlett2, Jonathan W Friedberg2. 1. Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI. paul_barr@urmc.rochester.edu. 2. Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
Abstract
PURPOSE: Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). PATIENTS AND METHODS: Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) receivedalisertib 50 mg twice a day for 7 days on 21-day cycles. RESULTS: Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. CONCLUSION:Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL.
RCT Entities:
PURPOSE: Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). PATIENTS AND METHODS: Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. RESULTS: Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. CONCLUSION:Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL.
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