1. A phase I trial of bortezomib in combination with everolimus for treatment of relapsed/refractory non-Hodgkin lymphoma.
- Author
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Hill, Brian T., Smith, Mitchell R., Shelley, Meredeth, Jagadeesh, Deepa, Dean, Robert M., Pohlman, Brad, Sweetenham, John W., Bolwell, Brian J., and Smith, Stephen D.
- Subjects
HODGKIN'S disease treatment ,LYMPHOBLASTIC leukemia treatment ,HEMATOPOIETIC system ,IMMUNOLOGIC diseases ,T-cell lymphoma - 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 5mg 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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