title: Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma.
abstract: Renal insufficiency (RI) is a frequent complication of multiple myeloma (MM) with negative consequences for patient survival. The improved clinical outcome with successive Total Therapy (TT) protocols was limited to patients without RI. We therefore performed a retrospective analysis of overall survival, progression-free survival and time to progression (TTP) of patients enrolled in TT2 and TT3 in relationship to RI present at baseline and pre-transplant. Glomerular filtration rate was graded in four renal classes (RCs), RC1-RC4 (RC1 ⩾90 ml/min/1.73 m(2), RC2 60-89 ml/min/1.73 m(2), RC3 30-59 ml/min/1.73 m(2) and RC4 <30 ml/min/1.73 m(2)). RC1-3 had comparable clinical outcomes while RC4 was deleterious, even after improvement to better RC after transplant. Among the 85% of patients with gene expression profiling defined low-risk MM, Cox regression modeling of baseline and pre-transplant features, which also took into consideration RC improvement and MM complete response (CR), identified the presence of metaphase cytogenetic abnormalities and baseline RC4 as independent variables linked to inferior TTP post-transplant, while MM CR reduced the risk of progression and TTP by more than 60%. Failure to improve clinical outcomes despite RI improvement suggested MM-related causes. Although distinguishing RC4 from RC<4, 46 gene probes bore no apparent relationship to MM biology or survival.
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: R
authors: R
authors: Khan
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: S
authors: S
authors: Apewokin
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: M
authors: M
authors: Grazziutti
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: S
authors: S
authors: Yaccoby
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: J
authors: J
authors: Epstein
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: F
authors: F
authors: van Rhee
authors: Cancer Research and Biostatistics, Seattle, WA, USA.
authors: A
authors: A
authors: Rosenthal
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: S
authors: S
authors: Waheed
authors: 1] Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA [2] Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC, USA.
authors: S
authors: S
authors: Usmani
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: S
authors: 0000000345477534
authors: S
authors: Atrash
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: S
authors: S
authors: Kumar
authors: Cancer Research and Biostatistics, Seattle, WA, USA.
authors: A
authors: A
authors: Hoering
authors: Cancer Research and Biostatistics, Seattle, WA, USA.
authors: J
authors: J
authors: Crowley
authors: Signal Genetics Inc, Carlsbad, CA, USA.
authors: J D
authors: JD
authors: Shaughnessy
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: B
authors: B
authors: Barlogie
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002097:C-Reactive Protein / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D015999:Multivariate Analysis; D010950:Plasma Cells / Q000166:cytology; D011379:Prognosis; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000008:administration & dosage; D051437:Renal Insufficiency / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D002097:C-Reactive Protein; D003404:Creatinine
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