The addition of cyclophosphamide to lenalidomide and dexamethasone in multiply relapsed/refractory myeloma patients; a phase I/II study

• Published in: British journal of haematology 2010-08, Vol.150 (3), p.326-333
• Main Authors: Schey, Stephen A., Morgan, Gareth J., Ramasamy, Karthik, Hazel, Beth, Ladon, Dariusz, Corderoy, Sophie, Jenner, Matthew, Phekoo, Karen, Boyd, Kevin, Davies, Faith E.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - toxicity; Biological and medical sciences; cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - toxicity; Dexamethasone - administration & dosage; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Hematologic Diseases - chemically induced; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Lenalidomide; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multiple Myeloma (MM); Multiple Myeloma - drug therapy; relapsed/refractory disease; Survival Analysis; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; Treatment Outcome
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2010.08250.x

Summary 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.