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Phase II Study Shows Activity of Aurora A Kinase Inhibitor Alisertib in Relapsed/Refractory Peripheral T-Cell Lymphoma

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Key Points

  • Alisertib produced responses in 30% of patients with peripheral T-cell non-Hodgkin lymphoma.
  • Response was not associated with aurora A kinase tumor levels.

In a phase II Intergroup trial (SWOG 1108) reported in the Journal of Clinical Oncology, Barr et al found that the aurora A kinase inhibitor alisertib produced responses in patients with relapsed/refractory peripheral T-cell non-Hodgkin lymphoma. Aurora A kinase is upregulated in highly proliferative lymphomas.

Study Details

In the study, 37 patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides received alisertib 50 mg twice a day for 7 days in 21-day cycles. Patients had peripheral T-cell lymphoma–not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), transformed mycosis fungoides (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Patients had a median age of 62 years and had received a median of three prior regimens, 65% were male, and 54% were refractory to their last regimen.

Response Rate

Response was observed in 30% of patients with peripheral T-cell lymphoma (complete response in 7%), with a median duration of response of 3 months (range 1–18 months). No responses were observed in patients with transformed mycosis fungoides. Aurora B kinase was more commonly overexpressed than aurora A kinase in tumor specimens. Analysis of aurora A kinase, aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression showed no association with response.

Adverse Events

The most common treatment-related adverse events of any grade were anemia (59%), thrombocytopenia (46%), fatigue (46%), and neutropenia (43%). The most common treatment-related grade 3 or 4 adverse events were neutropenia (32%), anemia (30%), and thrombocytopenia (24%); others included febrile neutropenia (14%), mucositis (11%), and rash (5%).

The investigators concluded: “Alisertib has antitumor activity in [peripheral T-cell lymphoma], 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 [peripheral T-cell lymphoma].”

Paul M. Barr, MD, of the University of Rochester, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by National Institutes of Health/National Cancer Institute Cooperative Group grants and National Clinical Trials Network grants. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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