Table 3.
Landmark Clinical Trials of Histone Deacetylase Inhibitors.
| Investigator [Ref.] Study |
Phase | Disease Status | #Prior Therapies Allowed | Treatment | Dosing Schedule of the HDACi | N | Survival End-Point (Months or %) | ORR | ≥VGPR Rate | Median Number of Prior Therapies | Prior Exposure | AEs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Siegel DS [46] VANTAGE-095 | IIb | RRMM | ≥2 | Vorinostat-BTZ | Vorinostat 400 mg PO days 1–14 q21days | 143 | PFS 3.1, OS 11.2 |
11.3% | 1% VGPR | 2 | BTZ-refractory 100%, IMiD-refractory 87% | SAE: 65% |
| Dimopoulos M [47] VANTAGE-088 | III | RRMM | 1–3 | Vorinostat-Vd vs. placebo-Vd | Vorinostat 400 mg PO days 1–14 q21days | 637 | mPFS 7.6 vs. 6.8, mOS NA vs. 28 |
56% vs. 40% | CR 7.9% vs. 5.3% | 2 | Previous BTZ 25% vs. 23% | SAE: 41.3% vs. 43.1% |
| San Miguel JF [48,49] PANORAMA 1 | III | RRMM | 1–3 | PanoVd vs. Placebo-Vd | Pano 20 mg PO days 1, 3, 5, 8, 10, 12 q21days | 768 | mPFS 12.1 vs. 8.1, mOS 40.3 vs. 35.8 |
61% vs. 55% | 28% vs. 16% | 2 | Previous BTZ 51% vs. 52% Previous AHCT 56% vs. 59% |
SAEs 60% vs. 42% |
Abbreviations: R: lenalidomide, d: low-dose dexamethasone, M: melphalan, Pano: panobinostat, mPFS: median progression-free survival, mOS: median overall survival, ORR: overall response rate, VGPR: very good partial response, CR: complete response, RRMM: relapse/refractory multiple myeloma, NDMM: newly diagnosed multiple myeloma, AE: adverse events, SAE: serious adverse events, G: grade, MTD: maximum tolerated dose, Cy: cyclophosphamide, V: bortezomib, AHCT: autologous hematopoietic cell transplantation, PO: per os (by mouth).