title: A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis.
abstract: Immunomodulatory drugs have been shown to be of benefit in relapsed/refractory immunoglobulin light-chain (AL) amyloidosis. We designed a prospective, multicentre phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with AL amyloidosis not eligible for autologous stem-cell transplantation. Twenty-eight patients were included in the study. Cardiac involvement was present in 23 patients; 14 of them had cardiac stage III. The overall haematological response rate was 46%, including complete and very good partial responses in 25% and 18% of patients respectively. Haematological response was mainly associated with absence of cardiac stage III and lower tumour burden. Organ response was observed in 46% of patients. After a median follow-up of 24 months, median progression-free and overall survival have not been reached, both being significantly longer in responders (P < 0·001 and P = 0·001 respectively). Seventeen patients have discontinued treatment, mostly due to amyloid-related death, disease progression or lack of response. Only 14% of the patients discontinued treatment due to therapy-related adverse events. Our results support the efficacy of this regimen, with high quality responses and prolonged survival, as well as its tolerability, in patients with AL amyloidosis not eligible for stem cell transplant and without advanced cardiac involvement (clinicaltrials.gov identifier: NCT01194791).
authors.affiliation: Amyloidosis and Myeloma Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Cibeira
authors.affiliation: ICO-Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Hospital Doce de Octubre, Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lahuerta
authors.affiliation: Hospital Clínico/Centro de Investigacion del Cáncer, Salamanca, Spain.
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Hospital La Fe, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.affiliation: Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernández
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Granell
authors.affiliation: Amyloidosis and Myeloma Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández de Larrea
authors.affiliation: Clínica Universidad de Navarra, CIMA, Pamplona, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.affiliation: Amyloidosis and Myeloma Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D007147:Immunoglobulin Light Chains; D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide; D000077269:Lenalidomide
keywords: AL amyloidosis; cyclophosphamide; dexamethasone; lenalidomide; untreated