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Clinical Trial
. 2010 Nov 1;28(31):4740-6.
doi: 10.1200/JCO.2010.29.2813. Epub 2010 Sep 13.

Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium

Sonali M Smith  1 , Koen van Besien, Theodore Karrison, Janet Dancey, Peter McLaughlin, Anas Younes, Scott Smith, Patrick Stiff, Eric Lester, Sanjiv Modi, L Austin Doyle, Everett E Vokes, Barbara Pro
Affiliations
Clinical Trial

Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium

Sonali M Smith et al. J Clin Oncol. .

Abstract

Purpose: Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas.

Patients and methods: We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas).

Results: Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis.

Conclusions: Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.

Trial registration: ClinicalTrials.gov NCT00290472.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
(A) Progression-free survival and (B) overall survival for patients with either diffuse large B-cell lymphoma (blue), follicular lymphoma (gold), and chronic lymphocytic leukemia/small lymphocytic lymphoma (gray).
See this image and copyright information in PMC

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