title: Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.
abstract: We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.
authors.affiliation: The Institute of Cancer Research, London, UK.|The Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Jones
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Cairns
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: W M
authors.initials: WM
authors.lastname: Gregory
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: C
authors.initials: C
authors.lastname: Collett
authors.affiliation: The Institute of Cancer Research, London, UK.|The Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: C
authors.identifier: 0000-0002-7190-0028
authors.initials: C
authors.lastname: Pawlyn
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sigsworth
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: A
authors.identifier: 0000-0003-3363-8417
authors.initials: A
authors.lastname: Striha
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: R
authors.initials: R
authors.lastname: Henderson
authors.affiliation: The Institute of Cancer Research, London, UK.|The Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: M F
authors.initials: MF
authors.lastname: Kaiser
authors.affiliation: Department of Haematology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jenner
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: G
authors.initials: G
authors.lastname: Cook
authors.affiliation: Centre for Clinical Haematology, Nottingham University Hospital, Nottingham, UK.
authors.forename: N H
authors.initials: NH
authors.lastname: Russell
authors.affiliation: Centre for Clinical Haematology, Nottingham University Hospital, Nottingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.affiliation: Heart of England NHS Foundation Trust, Birmingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: Pratt
authors.affiliation: Heart of England NHS Foundation Trust, Birmingham, UK.
authors.forename: B
authors.initials: B
authors.lastname: Kishore
authors.affiliation: Department of Haematology, East Kent Hospitals University NHS Foundation Trust, Kent, UK.
authors.forename: J
authors.initials: J
authors.lastname: Lindsay
authors.affiliation: Clinical Immunology, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
authors.forename: M T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: The Institute of Cancer Research, London, UK.|The Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: F E
authors.initials: FE
authors.lastname: Davies
authors.affiliation: The Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: K D
authors.initials: KD
authors.lastname: Boyd
authors.affiliation: University of Leeds, Leeds, UK.
authors.forename: R G
authors.initials: RG
authors.lastname: Owen
authors.affiliation: Department of Haematology, Newcastle University, Newcastle, UK.
authors.forename: G H
authors.initials: GH
authors.lastname: Jackson
authors.affiliation: The Institute of Cancer Research, London, UK.|The Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000069286:Bortezomib / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D009842:Oligopeptides; D013792:Thalidomide; D000077337:Vorinostat; D000069286:Bortezomib; C524865:carfilzomib; D000077269:Lenalidomide