A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma

T. E. Witzig, C. B. Reeder, B. R. Laplant, M. Gupta, P. B. Johnston, I. N. Micallef, L. F. Porrata, S. M. Ansell, J. P. Colgan, E. D. Jacobsen, I. M. Ghobrial, T. M. Habermann

Research output: Contribution to journalArticle

241 Scopus citations

Abstract

The phosphatidylinositol 3-kinase signal transduction pathway members are often activated in tumor samples from patients with non-Hodgkin's lymphoma (NHL). Everolimus is an oral agent that targets the raptor mammalian target of rapamycin (mTORC1). The goal of this trial was to learn the antitumor activity and toxicity of single-agent everolimus in patients with relapsed/refractory aggressive NHL. Patients received everolimus 10 mg PO daily. Response was assessed after two and six cycles, and then every three cycles until progression. A total of 77 patients with a median age of 70 years were enrolled. Patients had received a median of three previous therapies and 32% had undergone previous transplant. The overall response rate (ORR) was 30% (95% confidence interval: 20-41%), with 20 patients achieving a partial remission and 3 a complete remission unconfirmed. The ORR in diffuse large B cell was 30% (14/47), 32% (6/19) in mantle cell and 38% (3/8) in follicular grade 3. The median duration of response was 5.7 months. Grade 3 or 4 anemia, neutropenia and thrombocytopenia occurred in 14, 18 and 38% of patients, respectively. Everolimus has single-agent activity in relapsed/refractory aggressive NHL and provides proof-of-concept that targeting the mTOR pathway is clinically relevant.

Original languageEnglish (US)
Pages (from-to)341-347
Number of pages7
JournalLeukemia
Volume25
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • everolimus
  • large cell lymphoma
  • lymphoma
  • mTOR
  • mantle cell lymphoma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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