title: The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study.
abstract: We report the results of a Phase I/II dose escalation study to determine the maximum tolerated dose (MTD) of cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled in cohorts of 3, at five dose levels of cyclophosphamide to a maximum of 700 mg on days 1 and 8 of a 28-d cycle. Patients received lenalidomide 25 mg days 1-21 and dexamethasone 20 mg orally days 1-4 and 8-11. The MTD was 600 mg cyclophosphamide, days 1 and 8. Grade 3/4 haematological complications occurred in 26% of patients, grade 3/4 infection in 3% (both at 700 mg cyclophosphamide), with thromboembolic complications in 6% of patients. Overall complete response (CR) rate was 29%, very good partial response rate 7% and partial response rate 45% giving an overall response rate of 81%. After 21 months median follow-up, projected 2-year progression-free survival was 56%, with 80% overall survival at 30 months. Ten further patients were treated at MTD with a 40% CR rate. No dose reductions for any study drugs or deaths occurred during cycles 1-9. Lenalidomide, cyclophosphamide and dexamethasone is a safe, effective combination in relapsed myeloma inducing a high response rate, warranting further investigation in phase III trials.
authors.affiliation: Department of Haematological Medicine, King's College Hospital, London, UK. sschey@nhs.net
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Schey
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: Karthik
authors.initials: K
authors.lastname: Ramasamy
authors.forename: Beth
authors.initials: B
authors.lastname: Hazel
authors.forename: Dariusz
authors.initials: D
authors.lastname: Ladon
authors.forename: Sophie
authors.initials: S
authors.lastname: Corderoy
authors.forename: Matthew
authors.initials: M
authors.lastname: Jenner
authors.forename: Karen
authors.initials: K
authors.lastname: Phekoo
authors.forename: Kevin
authors.initials: K
authors.lastname: Boyd
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide; D000077269:Lenalidomide