title: Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis.
abstract: High-dose melphalan with stem-cell transplantation is believed to be the most effective treatment for systemic light-chain (AL) amyloidosis, but many patients are ineligible because of the extent of their disease, and treatment-related mortality (TRM) remains substantial. We report the use of a risk-adapted oral regimen of cyclophosphamide, thalidomide, and dexamethasone (CTD) or attenuated CTD (CTDa) in 75 patients with advanced AL amyloidosis, including 44 patients with clonal relapse after prior therapy. Fifty-one (68%) patients received CTD and 24 (32%) received CTDa. A hematologic response occurred in 48 (74%) of 65 evaluable patients, including complete responses in 14 (21%) and partial responses in 34 (53%) cases. Median estimated overall survival (OS) from commencement of treatment was 41 months, and from diagnosis median was not reached with a median follow-up of 22 months. Three-year estimated OS was 100% and 82% among complete and partial hematologic responders, respectively. Toxicity necessitating cessation of therapy occurred in 8% and was at least grade 2 in 52% of patients. TRM was 4%. The clonal response rates to CTD reported here are higher than any previously reported nontransplantation regimen in AL amyloidosis, and risk adaptation allows its use in poorer risk patients. CTD merits prospective randomized study.
authors.affiliation: National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Rowland Hill St, London NW3 2PF, UK. a.wechalekar@medsch.ucl.ac.uk
authors.forename: Ashutosh D
authors.initials: AD
authors.lastname: Wechalekar
authors.forename: Hugh J B
authors.initials: HJ
authors.lastname: Goodman
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
authors.forename: Mark
authors.initials: M
authors.lastname: Offer
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007147:Immunoglobulin Light Chains; D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide