Bortezomib,Vorinostat, and Dexamethasone Combination Therapy in Relapsed Myeloma: Results of the Phase 2 MUK four Trial |
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| Authors: | Sarah Brown Charlotte Pawlyn Avie-Lee Tillotson Debbie Sherratt Louise Flanagan Eric Low Gareth J Morgan Cathy Williams Martin Kaiser Faith E Davies Matthew W Jenner |
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| Institution: | 1. Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK;2. Myeloma Laboratory, The Institute of Cancer Research, Sutton, UK;3. Myeloma UK, Edinburgh, UK;4. Perlmutter Cancer Center, NYU Langone Health, New York, NY;5. Centre for Clinical Haematology, Nottingham University Hospitals, Nottingham, UK;6. Department of Haematology, Southampton General Hospital, Southampton, UK;1. Duke–NUS Medical School, Singapore;2. Haematology/Oncology Service, Department of Paediatric Subspecialties, KK Women’s and Children’s Hospital, Singapore;3. Division of Paediatric Haematology/Oncology, Department of Paediatrics, National University Hospital, Singapore;1. Real-world Evidence/Data Analytics Center of Excellence, Pharmerit International LP, Bethesda, MD;2. Market Access, Taiho Oncology, Princeton, NJ;3. Yale Cancer Center, Smilow Cancer Hospital at Yale New Haven, New Haven, CT;1. Department of Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey;2. Department of Hematology, Faculty of Medicine, Ondokuz May?s University, Samsun, Turkey;1. Chronic Disease Research Group, Minneapolis, Minneapolis Medical Research Foundation, Minneapolis, MN;2. Center for Observational Research, Amgen Inc, Thousand Oaks, CA;1. Nuclear Medicine, University of Brescia and Spedali Civili Brescia, Brescia, Italy;2. Health Physics Department, ASST-Spedali Civili, Brescia, Italy;1. Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;2. School of Medicine, Universidad Veracruzana, Veracruz, Mexico |
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| Abstract: | IntroductionOutcomes continue to improve in relapsed myeloma as more effective treatment options emerge. We report a multicenter single-arm phase 2 trial evaluating toxicity and efficacy of the histone deacetylase (HDAC) inhibitor vorinostat in combination with bortezomib and dexamethasone.Patients and MethodsSixteen patients who had received a median of 1 prior treatment line received bortezomib subcutaneously 1.3 mg/m2 days 1, 4, 8, and 11; dexamethasone 20 mg orally days 1-2, 4-5, 8-9, and 11-12; vorinostat 400 mg orally days 1-4, 8-11, and 15-18 of a 21-day cycle. After receipt of a minimum of 3 cycles of therapy, participants received maintenance vorinostat (400 mg days 1-4 and 15-18 of a 28-day cycle).ResultsOverall response was 81.3%: complete response occurred in 4 of 16, very good partial response in 2 of 16, and partial response 7 of 16. Clinical benefit response rate was 100%; median progression-free survival was 11.9 months. A total of 75% patients experienced a dose reduction or stopped treatment as a result of intolerability.ConclusionAlthough toxicity and dose reductions were observed, this study demonstrates that the combination of vorinostat, bortezomib, and dexamethasone is effective in relapsed myeloma with good response rates, suggesting there is an ongoing rationale for further optimization of HDAC inhibitor–based combinations in the treatment of myeloma to improve tolerability and enhance efficacy. |
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| Keywords: | Clinical trial HDAC inhibitor MM Proteasome inhibitor |
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