Vol 12, Supp. C (2021)
Case report
Published online: 2020-12-15

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The use of midostaurin in the treatment of advanced systemic mastocytosis

Marek Hus1, Aneta Szudy-Szczyrek1, Justyna Kozińska1, Oliwia Bachanek-Mitura1

Abstract

Systemic mastocytosis (SM) is a rare myeloproliferative neoplasms (MPN) characterized by clonal growth and accumulation of mast cells in various organs, mainly in the skin, bone marrow, liver, spleen, and lymph nodes. In its advanced form, SM leads to impairment of their function. The clinical course is highly variable, ranging from slow to very aggressive with progressive multi-organ failure and a significant risk of leukemic transformation. Advanced SM is an indication for cytoreductive therapy. So far, various treatment strategies have been used, including cladribine (2-CDA), imatinib, interferon alpha (IFN-α), as well as classic cytostatics (hydroxycarbamide, cytarabine or fludarabine). However, none of the options mentioned provided satisfactory response rates. Currently, high hopes are related to midostaurin — a multi-pathway tyrosine kinase inhibitor. The drug was approved for the treatment of advanced forms of SM by the US Food and Drug Administration (FDA) in April 2017 based on the satisfactory results of phase II clinical trial #CPKC412D2201. In this paper, we present case reports of two patients diagnosed with aggressive systemic mastocytosis (ASM) and systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) treated with midostaurin as part of the early access program.

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References

  1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. Blood. 2016; 128(3): 462–463.
  2. Lim KH, Tefferi A, Lasho TL, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood. 2009; 113(23): 5727–5736.
  3. Pardanani A. Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management. Am J Hematol. 2015; 90(3): 250–262.
  4. Horny HP, Akin C, Arber D, et al. Mastocytosis. In WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues; IARC Press: Lyon, France. ; 2017: 62–69.
  5. Kristensen T, Vestergaard H, Bindslev-Jensen C, et al. Mastocytosis Centre, Odense University Hospital (MastOUH). Sensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis. Am J Hematol. 2014; 89(5): 493–498.
  6. Jara-Acevedo M, Teodosio C, Sanchez-Muñoz L, et al. Detection of the KIT D816V mutation in peripheral blood of systemic mastocytosis: diagnostic implications. Mod Pathol. 2015; 28(8): 1138–1149.
  7. Arock M, Sotlar K, Akin C, et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia. 2015; 29(6): 1223–1232.
  8. Ustun C, Gotlib J, Popat U, et al. Consensus Opinion on Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis. Biol Blood Marrow Transplant. 2016; 22(8): 1348–1356.
  9. Lim KH, Pardanani A, Butterfield JH, et al. Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009; 84(12): 790–794.
  10. Barete S, Lortholary O, Damaj G, et al. Group AFIRMM (Association française pour les initiatives de recherche sur le mastocyte et les mastocytoses). Interest of interferon alpha in systemic mastocytosis. The French experience and review of the literature. Pathol Biol (Paris). 2004; 52(5): 294–299.
  11. Gallogly MM, Lazarus HM, Cooper BW. Midostaurin: a novel therapeutic agent for patients with FLT3-mutated acute myeloid leukemia and systemic mastocytosis. Ther Adv Hematol. 2017; 8(9): 245–261.
  12. Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis. N Engl J Med. 2016; 374(26): 2530–2541.
  13. Walker AR, Wang H, Walsh K, et al. Midostaurin, bortezomib and MEC in relapsed/refractory acute myeloid leukemia. Leuk Lymphoma. 2016; 57(9): 2100–2108.
  14. Pardanani A, Lim KH, Lasho TL, et al. Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies. Blood. 2009; 114(18): 3769–3772.
  15. Valent P, Akin C, Escribano L, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007; 37(6): 435–453.
  16. Valent P, Sperr WR, Akin C. How I treat patients with advanced systemic mastocytosis. Blood. 2010; 116(26): 5812–5817.



Hematology in Clinical Practice