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Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma
Author(s) -
Jonsdottir Gudbjorg,
Björkholm Magnus,
Turesson Ingemar,
Hultcrantz Malin,
Diamond Benjamin,
Porwit Anna,
Landgren Ola,
Kristinsson Sigurdur Y.
Publication year - 2021
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13650
Subject(s) - medicine , melphalan , multiple myeloma , myelodysplastic syndromes , cumulative incidence , myeloid leukemia , hematologic malignancy , cumulative dose , chemotherapy , lenalidomide , population , oncology , bone marrow , surgery , gastroenterology , cohort , environmental health
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.