Wahaib, K; Beggs, AE; Campbell, H; Kodali, L; Ford, PD
PURPOSE: The mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy, interaction potential, adverse effects, and place in therapy of panobinostat are reviewed.
SUMMARY: Panobinostat (Farydak, Novartis) is a novel pan-deacetylase inhibitor approved for use in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least two regimens containing an immunomodulatory drug and bortezomib. National Comprehensive Cancer Network (NCCN) guidelines recommend the use of panobinostat plus bortezomib and dexamethasone as a preferred regimen for previously treated multiple myeloma (MM). A Phase III trial comparing panobinostat or placebo use in combination with bortezomib and dexamethasone demonstrated improved median progression-free survival in the panobinostat group (11.99 months [95% CI, 10.33-12.94 months] versus 8.08 months [95% CI, 7.56-9.23 months]; hazard ratio, 0.63 [95% CI, 0.52-0.76]; p < 0.0001), as well as a significantly higher rate of complete or near complete response (27.6% [95% CI, 23.2-32.4%] versus 15.7% [95% CI, 12.2-19.8%]; p = 0.00006). Common grade 3 or 4 laboratory abnormalities and adverse events associated with panobinostat include thrombocytopenia, lymphopenia, diarrhea, asthenia, fatigue, and peripheral neuropathy.
CONCLUSION: Panobinostat is a promising alternative to well-studied, NCCN-recommended regimens for the treatment of RRMM. It has demonstrated efficacy when used in combination with bortezomib and dexamethasone for the treatment of patients with MM who have received at least two prior regimens including bortezomib and an immunomodulatory agent. Despite the observed benefits, concern regarding toxicity may limit panobinostat use in practice.