Phase II intergroup trial of alisertib in relapsed and refractory peripheral T-cell lymphoma and transformed Mycosis fungoides: SWOG 1108

Paul M. Barr, Hongli Li, Catherine S Perry, Daruka Mahadevan, Michael LeBlanc, Mansoor Ul Haq, Bryan D. Huber, Christopher R. Flowers, Nina D. Wagner-Johnston, Steven M. Horwitz, Richard I. Fisher, Bruce D. Cheson, Sonali M. Smith, Brad S. Kahl, Nancy L. Bartlett, Jonathan W. Friedberg

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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) 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.

Original languageEnglish (US)
Pages (from-to)2399-2404
Number of pages6
JournalJournal of Clinical Oncology
Volume33
Issue number21
DOIs
StatePublished - Jul 20 2015

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Barr, P. M., Li, H., Perry, C. S., Mahadevan, D., LeBlanc, M., Ul Haq, M., Huber, B. D., Flowers, C. R., Wagner-Johnston, N. D., Horwitz, S. M., Fisher, R. I., Cheson, B. D., Smith, S. M., Kahl, B. S., Bartlett, N. L., & Friedberg, J. W. (2015). Phase II intergroup trial of alisertib in relapsed and refractory peripheral T-cell lymphoma and transformed Mycosis fungoides: SWOG 1108. Journal of Clinical Oncology, 33(21), 2399-2404. https://doi.org/10.1200/JCO.2014.60.6327