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Acute myeloid leukemia

Second cancers in adults with acute promyelocytic leukemia treated with or without arsenic trioxide: a SEER-medicare analysis

Leukemia volume 34, pages 3082–3084 (2020)Cite this article

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Recently, Kayser et al. reported a significantly lower cumulative incidence of relapse in patients ≥ 70 years with newly-diagnosed acute promyelocytic leukemia (APL) treated with (N = 162) compared to without (N = 192) arsenic trioxide (ATO) [1], based on a multinational data collaboration. Induction deaths were lower and overall survival (OS) post-complete remission trended towards benefit with use of ATO. Eleven of 163 patients with available data developed a second neoplasm and none were treated with ATO. Therefore, this retrospective analysis of elderly patients with APL suggested ATO has a beneficial effect on efficacy of frontline therapy, in addition to a potential safety benefit regarding second malignancies.

In January 2018, the U.S. Food and Drug Administration (FDA) extended the indication for ATO (Trisenox; Teva Pharmaceuticals) to include its use in combination with all-trans retinoic acid (ATRA) for treatment of adults with newly-diagnosed low-risk APL, based in part on improvement in 2-year event-free survival with ATO + ATRA compared to chemotherapy + ATRA on Study APL0406 (NCT00482833) [2, 3]. During data review, FDA noted a potential signal for second malignancies with ATO use [4,5,6,7,8]. Epidemiologic studies have shown associations between exposure to inorganic arsenic and development of skin, lung, bladder, and potentially liver, kidney, and prostate cancers [9]. Therefore, the U.S. Prescribing Information for ATO includes a warning for carcinogenesis, with advice to monitor patients for development of second primary malignancies [3]. Since the incidence of second cancer following ATO treatment compared with other APL therapies is poorly understood, we performed a population-based analysis of second cancers in adults with APL treated with or without ATO.

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Fig. 1: Outcomes according to ATO treatment.

References

  1. Kayser S, Rahme R, Martinez-Cuadron D, Ghiaur G, Thomas X, Sobas M, et al. Outcome of older (>/=70 years) APL patients frontline treated with or without arsenic trioxide-an International Collaborative Study. Leukemia. 2020. https://doi.org/10.1038/s41375-020-0758-4. [Online ahead of print].

  2. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111–21.

    Article  CAS  Google Scholar 

  3. TRISENOX Prescribing Information. 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021248s018lbl.pdf.

  4. Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, et al. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017;129:1275–83.

    Article  CAS  Google Scholar 

  5. Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012;120:1570–80.

    Article  CAS  Google Scholar 

  6. Kutny MA, Alonzo TA, Gerbing RB, Wang YC, Raimondi SC, Hirsch BA, et al. Arsenic trioxide consolidation allows anthracycline dose reduction for pediatric patients with acute promyelocytic leukemia: report from the children’s oncology group Phase III Historically Controlled Trial AAML0631. J Clin Oncol. 2017;35:3021–9.

    Article  CAS  Google Scholar 

  7. Zhu H, Hu J, Chen L, Zhou W, Li X, Wang L, et al. The 12-year follow-up of survival, chronic adverse effects, and retention of arsenic in patients with acute promyelocytic leukemia. Blood. 2016;128:1525–8.

    Article  CAS  Google Scholar 

  8. Zhang Y, Zhang Z, Li J, Li L, Han X, Han L, et al. Long-term efficacy and safety of arsenic trioxide for first-line treatment of elderly patients with newly diagnosed acute promyelocytic leukemia. Cancer. 2013;119:115–25.

    Article  CAS  Google Scholar 

  9. IARC. Some Drinking-water Disinfectants and Contaminants, including Arsenic. IARC monographs on the evaluation of carcinogenic risks to humans. ume 84. Lyon, France: International Agency for Research on Cancer, World Health Organization; 2004. https://monographs.iarc.fr/wp-content/uploads/2018/06/mono84.pdf.

    Google Scholar 

  10. Eghtedar A, Rodriguez I, Kantarjian H, O’Brien S, Daver N, Garcia-Manero G, et al. Incidence of secondary neoplasms in patients with acute promyelocytic leukemia treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic acid plus arsenic trioxide. Leuk Lymphoma. 2015;56:1342–5.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge Kushal Naik MBBS, MPH, Ayushi Bhargava BDS, MPH, and Cameron Klig BA for assistance with analytics. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the National Cancer Institute; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database.

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Author notes

  1. The study was completed while Dr. Blumenthal was an FDA employee, but he has since changed affiliations and is now with Merck.

Authors and Affiliations

  1. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

    Kelly J. Norsworthy, Steven T. Bird, Albert B. Deisseroth, Richard Swain, Ann T. Farrell, R. Angelo de Claro & David J. Graham

  2. Acumen LLC, Burlingame, CA, USA

    Armen Avagyan, Yuchen Li, Sandia Akhtar, Jiemin Liao, Michael Wernecke & Thomas E. MaCurdy

  3. Oncology Center of Excellence, U.S. Food and Drug Administration, Silver Spring, MD, USA

    Meredith Chuk, Richard Pazdur & Gideon Blumenthal

  4. Department of Economics, Stanford University, Stanford, CA, USA

    Thomas E. MaCurdy

  5. Centers for Medicare & Medicaid Services, Washington, DC, USA

    Jeffrey A. Kelman

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Correspondence to Kelly J. Norsworthy.

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Norsworthy, K.J., Avagyan, A., Bird, S.T. et al. Second cancers in adults with acute promyelocytic leukemia treated with or without arsenic trioxide: a SEER-medicare analysis. Leukemia 34, 3082–3084 (2020). https://doi.org/10.1038/s41375-020-0905-y

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