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Phase 1 Trial Evaluating Vorinostat Plus Bortezomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
- Publication Year :
- 2020
-
Abstract
- Introduction Bortezomib plus lenalidomide and dexamethasone (VRD) is a standard induction therapy for newly diagnosed multiple myeloma (NDMM) patients. Given preclinical and clinical data suggesting the synergistic activity of the histone deacetylase inhibitor vorinostat with both bortezomib and lenalidomide for the treatment of multiple myeloma, we hypothesized that adding vorinostat to VRD (R2V2) would increase the rate and the quality of responses to induction treatment. Here we report the results of a phase 1 trial (NCT01038388) evaluating R2V2 as up-front treatment for NDMM patients. Patients and Methods R2V2 was tested as induction therapy in a dose-escalation phase 1 study in 30 NDMM patients deemed eligible for autologous stem-cell transplantation. Treatment consisted of 4 induction cycles with R2V2, followed by either autologous stem-cell transplantation or 4 additional R2V2 cycles and lenalidomide maintenance therapy. Results The maximum tolerated dose of vorinostat was 200 mg daily. The most common adverse events were gastrointestinal (87%), fatigue and peripheral neuropathy (60%), and thrombocytopenia (33%). R2V2 induced an objective response in 96% of patients, with 48% obtaining at least a complete remission. Median progression-free survival was 52 months, with 77% of patients alive at 5 years. Conclusion R2V2 as induction treatment for NDMM patients resulted in remarkable response rates at the cost of increased toxicity.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Inhibitor
Myeloma
Histone deacetylase
Quadruplet induction
Dexamethasone
Bortezomib
03 medical and health sciences
0302 clinical medicine
Maintenance therapy
Internal medicine
medicine
Humans
Adverse effect
Lenalidomide
Vorinostat
Multiple myeloma
Aged
business.industry
Hematology
Middle Aged
medicine.disease
Transplantation
030104 developmental biology
030220 oncology & carcinogenesis
Female
Multiple Myeloma
business
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....247ac64ff252c86ac5e974412ef88efd