Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: pharmacology and clinical outcomes.
Recently, outcomes for patients with multiple myeloma have improved dramatically due to improved and innovative therapies. However, most patients will either relapse or become refractory to current therapy. Thus, a significant unmet need remains for novel agents to treat this patient population. Panobinostat, a potent pan-deacetylase inhibitor with a unique mechanism of action targeting both epigenetic regulation of gene expression and protein metabolism, has preclinical synergy with a number of agents, including the proteasome inhibitor bortezomib. In a phase 3 trial of panobinostat with bortezomib and dexamethasone, addition of panobinostat significantly prolonged the median progression-free survival of patients with relapsed or relapsed and refractory multiple myeloma. This review focuses on clinical development of panobinostat, with particular emphasis on pharmacokinetics and adverse event management.
a Dana-Farber Cancer Institute , Harvard Medical School , Boston , MA , USA.
Paul G
PG
Richardson
b Winship Cancer Institute , Emory University , Atlanta , GA , USA.
R Donald
RD
Harvey
a Dana-Farber Cancer Institute , Harvard Medical School , Boston , MA , USA.
Jacob P
JP
Laubach
c Hematology Department , University Hospital , Nantes , France.
Philippe
P
Moreau
b Winship Cancer Institute , Emory University , Atlanta , GA , USA.
Sagar
S
Lonial
d CIMA, IDISNA , Clínica Universidad de Navarra , Pamplona , Spain.
Jesús F
JF
San-Miguel
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D000077767:Panobinostat; D012008:Recurrence
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat
bortezomib; deacetylase inhibitors; multiple myeloma; panobinostat; relapsed and refractory multiple myeloma