A phase I trial of bortezomib in combination with everolimus for treatment of relapsed/refractory non-Hodgkin lymphoma

Brian T. Hill, Mitchell R. Smith, Meredeth Shelley, Deepa Jagadeesh, Robert M. Dean, Brad Pohlman, John W. Sweetenham, Brian J. Bolwell, Stephen D. Smith

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5 mg everolimus daily with 1.3 mg/m2 bortezomib d1, 4, 8, and 11 every 21 days. Of 25 response-evaluable patients there was one complete response in a patient with MCL and three partial responses (two MCL, one FL) for an overall response rate of 16%. In conclusion, the combination of everolimus and bortezomib results in dose limiting thrombocytopenia, but is tolerable. This combination has limited clinical activity in heavily pretreated NHL.

Original languageEnglish (US)
Pages (from-to)690-694
Number of pages5
JournalLeukemia and Lymphoma
Volume59
Issue number3
DOIs
StatePublished - Mar 4 2018
Externally publishedYes

Keywords

  • chemotherapeutic approaches
  • Lymphoma and Hodgkin disease
  • signaling therapies

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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