title: A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis.
abstract: Despite improvements in therapy amyloid light-chain (AL) amyloidosis, there are few studies comparing different regimens. Here we present a matched comparison with 69 patients in each cohort examining upfront therapy with cyclophosphamide, bortezomib and dexamethasone (CVD) vs cyclophosphamide, thalidomide and dexamethasone (CTD). On an intention-to-treat basis, the overall response rates were 71.0% vs 79.7% in the CVD and CTD arms, respectively, (P=0.32). A higher complete response (CR) rate was observed in the CVD arm (40.5%) vs CTD (24.6%), P=0.046. One-year overall survival (OS) was 65.2% and 66.7% for CVD and CTD, respectively (P=0.87). The median progression-free survival (PFS) was 28.0 and 14.0 m for CVD and CTD, respectively (P=0.039). In a landmark analysis assessing outcomes performed at 6 months, the CR rate with CVD was 59.6% vs 34.0% for CTD (P=0.03). The 1-year OS was 96% with CVD and 92% with CTD (P=0.40). The median PFS with CVD was not reached and was 19.2 m with CTD, P=0.028). In summary, both regimens are unable to overcome the high rate of early deaths in AL amyloidosis. However, CVD correlates with improved depth of response and superior PFS supporting its use in the frontline setting. Further optimisation and better supportive-care strategies are required to increase the proportion of patients fully benefiting from therapy.
authors.affiliation: 1] National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK [2] Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: C P
authors.initials: CP
authors.lastname: Venner
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Gillmore
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sachchithanantham
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Mahmood
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Lane
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Foard
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Rannigan
authors.affiliation: 1] National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK [2] Department of Clinical Haematology, Manchester Royal Infirmary, Central Manchester University Hospitals, Manchester, UK.
authors.forename: S D J
authors.initials: SD
authors.lastname: Gibbs
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Pinney
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Whelan
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lachmann
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
authors.affiliation: National Amyloidosis Centre, Department of Medicine, University College London Medical School, Royal Free Hospital Campus, London, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Wechalekar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D007147:Immunoglobulin Light Chains; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide