title: Phase II study of melphalan, thalidomide and prednisone combined with oral panobinostat in patients with relapsed/refractory multiple myeloma.
abstract: The combination of melphalan, prednisone and thalidomide (MPT) has demonstrated efficacy and acceptable toxicity in newly diagnosed and relapsed/refractory patients with multiple myeloma (MM). Panobinostat is a potent oral pan-deacetylase inhibitor (pan-DACi). In preclinical and clinical studies, panobinostat showed good anti-myeloma activity in combination with several agents. This phase II study evaluated the combination of a fixed dose of MPT with escalating doses of panobinostat (three times weekly for 3 weeks, followed by a 9-day rest period) in relapsed/refractory MM. We used a two-stage design to determine whether the combination was safe and effective. At least a partial response was observed in 38.5% of patients. The maximum tolerated dose of panobinostat in combination with MPT could not be determined due to the high rate of dose-limiting toxicities experienced with panobinostat at doses of 10 and 15 mg. The most common grade 3/4 adverse events were neutropenia (71%) and thrombocytopenia (35.5%). In conclusion, MPT in combination with panobinostat three times weekly for 3 weeks followed by a 9-day rest period is not well tolerated in patients with relapsed/refractory MM. Future studies should evaluate alternative dose schedules of panobinostat.
authors.affiliation: Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy. m.offidani@ospedaliriuniti.marche.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Claudia
authors.initials: C
authors.lastname: Polloni
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.forename: Stelvio
authors.initials: S
authors.lastname: Ballanti
authors.forename: Stefano
authors.initials: S
authors.lastname: Pulini
authors.forename: Massimo
authors.initials: M
authors.lastname: Catarini
authors.forename: Francesco
authors.initials: F
authors.lastname: Alesiani
authors.forename: Laura
authors.initials: L
authors.lastname: Corvatta
authors.forename: Silvia
authors.initials: S
authors.lastname: Gentili
authors.forename: Patrizia
authors.initials: P
authors.lastname: Caraffa
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Pietro
authors.initials: P
authors.lastname: Leoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D000077767:Panobinostat; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006877:Hydroxamic Acids; D007211:Indoles; D013792:Thalidomide; D000077767:Panobinostat; D008558:Melphalan; D011241:Prednisone