A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma |
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| Authors: | Victor Yazbeck Danielle Shafer Edward B Perkins Domenico Coppola Lubomir Sokol Kristy L Richards Thomas Shea Jia Ruan Samir Parekh Roger Strair Christopher Flowers David Morgan Maciej Kmieciak Prithviraj Bose Amy Kimball Ashraf Z Badros Rachid Baz Hui-Yi Lin Beata Holkova |
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| Institution: | 1. Massey Cancer Center, Virginia Commonwealth University, Richmond, VA;2. Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA;3. Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL;4. Department of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, FL;5. Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC;6. Department of Medicine, Weill Cornell Medical College, Cornell University, New York, NY;7. Department of Oncology, Montefiore Medical Center, Bronx, NY;8. Cancer Institute of New Jersey, New Brunswick, NJ;9. Winship Cancer Institute of Emory University, Atlanta, GA;10. Vanderbilt-Ingram Cancer Center, Nashville, TN;11. Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, MD;12. Department of Biostatistics and Biomedical Informatics, H. Lee Moffitt Cancer Center, Tampa, FL;13. Department of Blood and Marrow Transplantation and Cellular Immunology, H. Lee Moffitt Cancer Center, Tampa, FL;14. Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA;15. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA;16. Institute for Molecular Medicine, Virginia Commonwealth University, Richmond, VA |
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| Abstract: | BackgroundThe proteasome inhibitor bortezomib has demonstrated marked preclinical activity when combined with the histone deacetylase inhibitor vorinostat in leukemia, multiple myeloma, and mantle cell lymphoma (MCL) cells. The present study evaluated the efficacy and safety of the combination in patients with relapsed or refractory MCL and diffuse large B-cell lymphoma (DLBCL).Patients and MethodsThe present multicenter, nonrandomized phase II trial used a Simon 2-stage design with 3 cohorts: cohort A, MCL with no previous bortezomib (including untreated MCL); cohort B, MCL with previous bortezomib; and cohort C, relapsed or refractory DLBCL with no previous bortezomib. Vorinostat (400 mg) was administered orally on days 1 to 5 and 8 to 12 before bortezomib (1.3 mg/m2), which was administered intravenously on days 1, 4, 8, and 11 of each 21-day cycle.ResultsFor the 65 treated patients (22 in cohort A, 4 in cohort B, and 39 in cohort C), the overall response rate was 31.8%, 0%, and 7.7%, respectively. The median progression-free survival was 7.6 months for cohort A and 1.8 months for cohort C. In cohort A, 7 patients had a partial response (PRs), 5 had stable disease (SD), 7 had progressive disease (PD), 1 was not assessed, and 2 were not evaluable. In cohort B, 2 had SD and 2 had PD. In cohort C, 3 had a PR, 8 had SD, 23 had PD, and 5 were not assessed. Baseline NF-κB activation, measured as nuclear RelA by immunohistochemistry, did not correlate with clinical response.ConclusionThe combination of bortezomib and vorinostat is safe and has modest activity in MCL and limited activity in DLBCL. |
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| Keywords: | Clinical trial DLBCL Histone deacetylase inhibitor MCL Proteasome inhibitors |
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