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Multicenter Study
. 2021 Aug;107(2):275-282.
doi: 10.1111/ejh.13650. Epub 2021 May 28.

Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma

Gudbjorg Jonsdottir  1   2 , Magnus Björkholm  3 , Ingemar Turesson  4 , Malin Hultcrantz  3   5 , Benjamin Diamond  5 , Anna Porwit  6 , Ola Landgren  7 , Sigurdur Y Kristinsson  1   3
Affiliations
Multicenter Study

Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma

Gudbjorg Jonsdottir et al. Eur J Haematol. 2021 Aug.

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.

Keywords: acute myeloid leukemia/myelodysplastic syndromes; alkylating therapy; melphalan; multiple myeloma; second malignancies.

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Conflict of interest statement

CONFLICT OF INTEREST

O.L has received honoraria for scientific talks and/or served on advisory boards for Adaptive, Amgen, Celgene, Janssen, BMS, and Takeda and has served as a member of independent data monitoring committees for Janssen, Takeda, Merck, and Theradex. All the other authors declare no conflicts of interest. M.B reports the following, all outside of the submitted work: research funding from Takeda; member of independent data monitoring committee for Mundipharma; Member of grant committee for Incyte; lecture honoraria from Astra-Zeneca, Roche, Pfizer and BMS.

References

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