title: Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival.
abstract: Bortezomib has shown great promise in the treatment of amyloid light-chain (AL) amyloidosis. We present our experience of 43 patients with AL amyloidosis who received cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or at relapse. Of these, 74% had cardiac involvement and 46% were Mayo Cardiac Stage III. The overall hematologic response rate was 81.4%, including complete response (CR) in 41.9% and very good partial response with >90% decrease in difference between involved/uninvolved light chain (VGPR-dFLC) in 51.4%. Patients treated upfront had higher rates of CR (65.0%) and VGPR-dFLC (66.7%). The estimated 2-year progression-free survival was 66.5% for patients treated upfront and 41.4% for relapsed patients. Those attaining a CR or VGPR-dFLC had a significantly better progression-free survival (P=.002 and P=.026, respectively). The estimated 2-year overall survival was 97.7% (94.4% in Mayo Stage III patients). CVD is a highly effective regimen producing durable responses in AL amyloidosis; the deep clonal responses may overcome poor prognosis in advanced-stage disease.
authors.affiliation: National Amyloidosis Centre, University College London Medical School, Royal Free Hospital Campus, London, United Kingdom. c.venner@ucl.ac.uk
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Venner
authors.forename: Thirusha
authors.initials: T
authors.lastname: Lane
authors.forename: Darren
authors.initials: D
authors.lastname: Foard
authors.forename: Lisa
authors.initials: L
authors.lastname: Rannigan
authors.forename: Simon D J
authors.initials: SD
authors.lastname: Gibbs
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Pinney
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Whelan
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
authors.forename: Julian D
authors.initials: JD
authors.lastname: Gillmore
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Ashutosh D
authors.initials: AD
authors.lastname: Wechalekar
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000188:drug therapy* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D060965:Clonal Evolution / Q000187:drug effects*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000682:Amyloid; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide