title: Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma.
abstract: Sixty-four transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) received carfilzomib (days 1, 2, 8, 9, 15, 16), 300 mg/m(2) cyclophosphamide (days 1, 8, 15), 100 mg thalidomide (days 1-28) and 40 mg dexamethasone (days 1, 8, 15, 22) in 28-day cycles (CYKLONE regimen). Carfilzomib was dose-escalated to 15/20, 20/27, 20/36 and 20/45 mg/m(2) to determine the maximum tolerated dose (MTD), which was 20/36 mg/m(2) . Regardless of attribution, common Grade 3 or higher adverse events were lymphopenia (38%), neutropenia (23%) and anaemia (20%). All peripheral neuropathy (31%) was Grade 1 and considered most likely to be thalidomide-related. Common cardiac or pulmonary events of any grade in ≥5% of patients included dyspnoea (20%) and cough (6%). Overall (N = 64), 91% of patients achieved a best response of partial response or better across all cycles of treatment, including five patients with complete responses. At the MTD (n = 29), 59% of patients achieved a very good partial response or better after four cycles (primary end point). Stem cell collection was successful in all patients in whom it was attempted (n = 42). Progression-free survival and overall survival at 24 months was 76% and 96%, respectively (median follow-up of 17·5 months). CYKLONE appears highly efficacious in NDMM patients, with manageable toxicities.
authors: Mayo Clinic, Scottsdale, AZ, USA.
authors: Joseph R
authors: JR
authors: Mikhael
authors: Craig B
authors: CB
authors: Reeder
authors: Edward N
authors: EN
authors: Libby
authors: Luciano J
authors: LJ
authors: Costa
authors: P Leif
authors: PL
authors: Bergsagel
authors: Francis
authors: F
authors: Buadi
authors: Angela
authors: A
authors: Mayo
authors: Sravan K
authors: SK
authors: Nagi Reddy
authors: Katherine
authors: K
authors: Gano
authors: Amylou C
authors: AC
authors: Dueck
authors: A Keith
authors: AK
authors: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D009842:Oligopeptides / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone; D003520:Cyclophosphamide
keywords: clinical studies; clinical trials; experimental therapies; multiple myeloma; myeloma therapy