Gudbjorg Jonsdottir1,2, Magnus Björkholm3, Ingemar Turesson4, Malin Hultcrantz3,5, Benjamin Diamond5, Anna Porwit6, Ola Landgren7, Sigurdur Y Kristinsson1,3. 1. Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2. Department of Hematology, Oncology, Blood and Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. 3. Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. 4. Department of Hematology, Skåne University Hospital, Malmö, Sweden. 5. Myeloma Service, Memorial Sloan-Kettering Center, New York, NY, USA. 6. Division of Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden. 7. Myeloma Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Abstract
OBJECTIVES: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM). METHODS: We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis. RESULTS: The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7-5.2; P < .001) among cases (median 988 mg; IQR 644-1640) compared with controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8-5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy. CONCLUSION: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.
OBJECTIVES: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM). METHODS: We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis. RESULTS: The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7-5.2; P < .001) among cases (median 988 mg; IQR 644-1640) compared with controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8-5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy. CONCLUSION: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.
Authors: Mirian Brink; Monique C Minnema; Otto Visser; Mark-David Levin; Eduardus F M Ward Posthuma; Annemiek Broijl; Pieter Sonneveld; Marjolein van der Klift; Wilfried W H Roeloffzen; Matthijs Westerman; Cleo R van Rooijen; Paul A F Geerts; Sonja Zweegman; Niels W C J van de Donk; Avinash G Dinmohamed Journal: Blood Cancer J Date: 2022-03-15 Impact factor: 11.037