title: Risks, severity and timing of infections in patients with multiple myeloma: a longitudinal cohort study in the era of immunomodulatory drug therapy.
abstract: We defined the epidemiology and clinical predictors of infection in patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous haematopoietic stem cell transplant (ASCT) in a large longitudinal cohort study. Clinical and microbiology records of patients with MM diagnosed between January 2008 and December 2012 were reviewed to capture patient demographics, characteristics of myeloma and infections (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of infection. One hundred and ninety-nine patients with MM with 771 episodes of infection were identified. 44·6% of infections were clinically defined, 35·5% were microbiologically defined and 19·9% were fever of unknown focus. There was a bimodal peak in incidence of bacterial (4-6 and 70-72 months) and viral infections (7-9 and 52-54 months) following disease diagnosis. Chemotherapy regimens high-dose melphalan [hazard ratio (HR) = 2·07], intravenous cyclophosphamide (HR = 1·96) and intensive combination systemic chemotherapy (HR = 1·86) and cumulative doses of corticosteroid (HR = 3·06 at highest dose) were independently associated with increased risk of infection overall (P < 0·05). IMiDs and PI and other clinical factors were not independently associated with increased risk of infection. New approaches to prevention and treatment of infection should focus upon identified periods of risk and treatment-related risk factors.
authors.affiliation: Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Teh
authors.affiliation: Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Vic., Australia.|Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harrison
authors.affiliation: Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Worth
authors.affiliation: Victorian Infectious Diseases Service, Doherty Institute for Infection and Immunity, Parkville, Vic., Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.|Victorian Infectious Diseases Service, Doherty Institute for Infection and Immunity, Parkville, Vic., Australia.
authors.forename: Karin A
authors.initials: KA
authors.lastname: Thursky
authors.affiliation: Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.|Victorian Infectious Diseases Service, Doherty Institute for Infection and Immunity, Parkville, Vic., Australia.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Slavin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D064592:Autografts; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects*; D007239:Infections / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology / Q000628:therapy*; D012307:Risk Factors
chemical_list: D000305:Adrenal Cortex Hormones; D007155:Immunologic Factors; D003520:Cyclophosphamide; D008558:Melphalan
keywords: immunomodulatory drugs; infection; multiple myeloma; risks