Additional therapeutic options are needed for relapsed and refractory multiple 
myeloma (RRMM). We present data from a phase 1b, open-label, dose-escalation 
study (NCT01965353) of 20 patients with RRMM (median age: 63 years [range: 
50-77]) and a median of four prior regimens (range: 2-14); 85% had refractory 
disease (lenalidomide [80%]; bortezomib [75%]; lenalidomide and bortezomib 
[50%]). Patients received a median of six cycles (range: 1-74) of panobinostat 
(10 or 15 mg), lenalidomide 15 mg, bortezomib 1 mg/m2, and dexamethasone 20 mg 
(pano-RVd). Median follow-up was ~14 months. Six dose-limiting toxicities were 
reported (mostly hematological); maximum tolerated dose of panobinostat (primary 
endpoint) was 10 mg. Most common adverse events (AEs) were diarrhea (60%) and 
peripheral neuropathy (60%); all grade 1/2. Grade 3/4 AEs occurred in 80% of 
patients and included decreased neutrophil (45%), platelet (25%) and white blood 
cell (25%) counts, anemia (25%) and hypophosphatemia (25%). No treatment-related 
discontinuations or mortality occurred. In evaluable patients (n = 18), overall 
response rate was 44%, and clinical benefit rate was 61%. Median duration of 
response was 9.2 months; progression-free survival was 7.4 months; overall 
survival was not reached. Pano-RVd proved generally well-tolerated and 
demonstrated potential to overcome lenalidomide and/or bortezomib resistance.