Page 225 - Haematologica April 2020

Plasma Cell Disorders
Fractures and survival in multiple myeloma: results from a population-based study
Sigrun Thorsteinsdottir,1,2 Gauti Gislason,2 Thor Aspelund,3 Ingigerdur Sverrisdottir,1,2 Ola Landgren,4 Ingemar Turesson,5 Magnus Björkholm6 and Sigurður Y. Kristinsson1,2
1Department of Internal Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 4Myeloma Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 5Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmo, Sweden and 6Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
ABSTRACT
Multiple myeloma causes lytic bone lesions and fractures. The impact of fractures on multiple myeloma (MM) survival is unclear. The aim of this study was to evaluate the effect of fractures on survival in MM using data from MM patients diagnosed in Sweden in the years 1990-2013, identified from the Swedish Cancer Registry. Information on date of birth, MM diagnosis, fractures, and death was collected from central registries. A Cox regression model was used to compare survival in patients with and without a fracture at MM diagnosis and another Cox model was used with fracture as a time-dependent variable to assess the effect of fracture on survival after MM diagnosis. Results were adjusted for age, sex, year of diagnosis, and previous fractures. A total of 14,013 patients were diagnosed with MM during the study, of whom 1,213 (8.7%) were diagnosed with a fracture at MM diagnosis, and 3,235 (23.1%) after diag- nosis. Patients with a fracture at diagnosis were at a significantly increased risk of death (hazard ratio=1.28; 95% confidence interval: 1.19-1.37). The risk of death was significantly increased in patients with a fracture after MM diagnosis (2.00; 1.90-2.10). The impact of fractures on survival did not change significantly between the two calendar periods 1990-1999 and 2000-2013 (0.98; 0.89-1.08). Our large study shows that MM patients with fractures are at a significantly increased risk of dying compared to those without fractures, which stresses the importance of preventing bone dis- ease in MM.
Introduction
Multiple myeloma (MM) is a malignant neoplasm of plasma cells in the bone marrow.1,2 Skeletal abnormalities are found in the majority of MM patients at the time of diagnosis, and manifestations of bone disease in MM include osteolytic lesions, osteopenia/osteoporosis, and fractures.3-5 Bone disease can be painful and reduces quality of life in MM patients.6,7 In MM bone disease, the interaction between malignant plasma cells and the bone microenvironment leads to osteoclas- tic bone destruction, reduced osteoblast function, and blocking of bone repair.8,9 This imbalance, along with decreased bone mineral density and treatment-related factors such as treatment with glucocorticoids, can lead to fractures in MM.5,10,11 In a population-based retrospective study, MM patients were found to have a 9-fold increase in risk of fractures after MM diagnosis, as compared to expected fracture rates in the population.5 To prevent skeletal-related events, treatment with bispho- sphonates is recommended for most patients with MM, and treatment with zole- dronic acid has been reported to improve overall survival in MM patients.12,13
Previous studies have shown that skeletal-related events (radiation to the bone, a pathologic or osteoporotic fracture, hypercalcemia, spinal cord compression, or sur- gery to the bone) are associated with reduced survival in both breast cancer and
Ferrata Storti Foundation
Haematologica 2020 Volume 105(4):1067-1073
Correspondence:
SIGRUN THORSTEINSDOTTIR
sth314@hi.is
Received: June 18, 2019. Accepted: November 28, 2019. Pre-published: December 2, 2019.
doi:10.3324/haematol.2019.230011
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/4/1067
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