Breast Isolated FLT3 Positive AML Relapse Treated with Gilteritinib in Monotherapy: Long- Term Follow-Up and Review of the Literature
Main Article Content
Abstract
Extramedullary relapse of acute myeloid leukemia (AML) is a relatively common occurrence, with the FMS-like tyrosine kinase 3 (FLT3) mutation being a significant risk factor. While gilteritinib is approved for treating relapsed/refractory FLT3+ AML, its effectiveness in extramedullary relapse is still not well established. We report the case of a 69-year-old woman diagnosed with therapy-related nucleophosmin-1 (NPM1) and FLT3-internal tandem duplication (FLT3-ITD) positive AML. She was initially treated with induction and consolidation therapy using CPX-351 (liposomal daunorubicin plus cytarabine) and subsequently received off-label azacitidine maintenance. Although she achieved complete remission with persistent measurable residual disease, 19 months later she experienced an isolated breast relapse of FLT3-ITD+ AML. The patient was treated with single agent gilteritinib, which led to a rapid and sustained complete regression of the breast nodule, maintained after 44 courses of treatment. This case demonstrates that target therapy with gilteritinib can be an effective option for isolated extramedullary relapse of FLT3-ITD+ AML.
Article Details
How to Cite
ARRIGO, Giulia et al.
Breast Isolated FLT3 Positive AML Relapse Treated with Gilteritinib in Monotherapy: Long- Term Follow-Up and Review of the Literature.
Medical Research Archives, [S.l.], v. 13, n. 5, may 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6559>. Date accessed: 21 june 2025.
doi: https://doi.org/10.18103/mra.v13i5.6559.
Section
Case Reports
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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25. Yan C, Zhou JL, Wu JH, Zhang JZ. Case Report Synchronous Granulocytic Sarcoma of the Breast and Spine: A Case Report and Review of the Literature. Vol 121.; 2008.
26. Gomaa W GAEEBKGA. Primary myeloid sarcoma of the breast: a case report and review of literature. J Microsc Ultrastruct 2018;6(4):212–4.
27. Shallis RM, Gale RP, Lazarus HM, et al. Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved. Blood Rev. 2021;47. doi:10.1016/j.blre.2020.100773
28. Yui J MMPMGNAKAEM et al. Myeloid sarcoma: the Mayo Clinic experience of ninety six case series. Blood 2016 Dec 2;128(22):2798.
29. Sharma A, Das AKr, Pal S, Bhattacharyya S. Fine-needle aspiration cytology of granulocytic sarcoma presenting as a breast lump – Report of a rare case with a comprehensive literature search. J Lab Physicians. 2018;10(01):113-115. doi:10.4103/jlp. jlp_114_17
30. Jelić-Puškarić B OKSPAOKDKSIJB. Myeloid sarcoma involving the breast. Coll Antropol 2010;34(2):641-4.
31. Zhang XH ZRLY. Granulocytic sarcoma of abdomen in acute myeloid leukemia patient with inv(16) and t(6;17) abnormal chromosome: case report and review of literature. Leuk Res 2010;34(7):958–61.
32. Ganzel C, Lee JW, Fernandez HF, et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021;5(22):4560-4568. doi:10.1182/bloodadvances.2021004999
33. Heuser M, Ofran Y, Boissel N, et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Annals of Oncology. 2020;31(6):697-712. doi:10.1016/j.annonc.2020.02.018
34. Cunningham I, Kohno B. 18FDG-PET/CT: 21st century approach to leukemic tumors in 124 cases. Am J Hematol. 2016;91(4):379-384. doi:10.1002/ajh.24287
35. Grunwald MR, Levis MJ. FLT3 tyrosine kinase inhibition as a paradigm for targeted drug development in acute myeloid leukemia. Semin Hematol. 2015;52(3): 193-199. doi:10.1053/j.seminhematol.2015.03.004
36. Urbino I, Secreto C, Olivi M, et al. Evolving therapeutic approaches for older patients with acute myeloid leukemia in 2021. Cancers (Basel). 2021;13(20). doi:10.3390/cancers13205075
37. Francesco Angotzi EBCSMBGGM et al. 1523 Disease Course and Treatment Patterns of Acute Myeloid Leukemia with FLT3 Mutations and Myeloid Sarcoma Reveal High Efficacy of Gilteritinib: A Multicentric Retrospective Study. ASH oral and poster abstract
2. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867
3. Pollyea DA, Bixby D, Perl A, et al. Acute Myeloid Leukemia, Version 2.2021 Featured Updates to the NCCN Guidelines. JNCCN Journal of the National Comprehensive Cancer Network. 2021;19(1):16-27. doi:10.6004/JNCCN.2021.0002
4. Welch JS, Ley TJ, Link DC, et al. NIH Public Access. 2013;150(2):264-278. doi:10.1016/j.cell.2012.06.023.
5. Papaemmanuil E, Ph D, Gerstung M, et al. Europe PMC Funders Group Genomic Classification and Prognosis in Acute Myeloid Leukemia. 2016;374(23):2209-2221. doi:10.1056/NEJMoa1516192.Genomic
6. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3 -Mutated AML . New England Journal of Medicine. 2019;381(18):1728-1740. doi:10.1056/nejmoa1902688
7. Patel JP, Gönen M, Figueroa ME, et al. Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia. New England Journal of Medicine. 2012;366(12):1079-1089. doi:10.1056/nejmoa1112304
8. Kiyoi H, Naoe T, Nakano Y, et al. Prognostic Implication of FLT3 and N-RAS Gene Mutations in Acute Myeloid Leukemia.
9. Fergun Yilmaz A, Saydam G, Sahin F, Baran Y. Granulocytic Sarcoma: A Systematic Review. Vol 3.; 2013. www.AJBlood.us/
10. Solh M, Solomon S, Morris L, Holland K, Bashey A. Blood Reviews Extramedullary acute myelogenous leukemia. YBLRE. 2016;30(5):333-339. doi:10.1016/j.blre.2016.04.001
11. Bourlon C, Lipton JH, Deotare U, et al. Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1. Eur J Haematol. 2017;99(3):234-239. doi:10.1111/ejh.12909
12. Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood. 2011;118(14):3785-3793. doi:10.1182/blood-2011-04-347229
13. Kida M, Kuroda Y, Kido M, Chishaki R, Kuraoka K, Ito T. Successful treatment with gilteritinib for isolated extramedullary relapse of acute myeloid leukemia with FLT3-ITD mutation after allogeneic stem cell transplantation. Int J Hematol. 2020;112(2):243-248. doi:10.1007/s12185-020-02855-4
14. Kumode T, Rai S, Tanaka H, et al. Targeted therapy for medullary and extramedullary relapse of FLT3-ITD acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation. Leuk Res Rep. 2020;14(August):100219. doi:10.1016/j.lrr.2020.100219
15. Perrone S, Ortu La Barbera E, Viola F, et al. A Relapsing Meningeal Acute Myeloid Leukaemia FLT3-ITD+ Responding to Gilteritinib. Chemotherapy. 2021;66(4):134-138. doi:10.1159/000518356
16. Kim RS, Yaghy A, Wilde LR, Shields CL. An Iridociliochoroidal Myeloid Sarcoma Associated with Relapsed Acute Myeloid Leukemia with FLT3-ITD Mutation, Treated with Gilteritinib, an FLT3 Inhibitor. JAMA Ophthalmol. 2020;138(4):418-419. doi:10.1001/jamaophthalmol.2020.0110
17. Ji Y, Wan Z, Yang J, Hao M, Liu L, Qin W. The safety and efficacy of the re-administration of gilteritinib in a patient with FLT3-mutated R/R AML with CNS relapse: a case report. Front Oncol. 2024;14. doi:10.3389/fonc.2024.1402970
18. Nicolas Vignal LKELACHJS et al. Favorable pharmacokinetic and pharmacodynamic properties of gilteritinib in cerebrospinal fluid: a potential effective treatment in relapsing meningeal acute myeloid leukemia FLT3-ITD patients. Haematologica | 108 September 2023.
19. McMahon CM, Canaani J, Rea B, et al. Gilteritinib induces differentiation in relapsed and refractory FLT3-mutated acute myeloid leukemia. Blood Adv. 2019;3(10):1581-1585. doi:10.1182/bloodadvances.2018029496
20. Krönke J, Bullinger L, Teleanu V, et al. Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia. Blood. 2013;122(1):100-108. doi:10.1182/blood-2013-01-479188
21. Wei AH, Döhner H, Pocock C, et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. New England Journal of Medicine. 2020;383(26):2526-2537. doi:10.1056/nejmoa2004444
22. Burns A. Observations of surgical anatomy, head and neck. Edinburgh: Thomas Royce; 1811 p 364–6.
23. King A. A case of chloroma. . Monthly J Med 1853;17:97.
24. Dock G. Chloroma and its relation to leukemia. Am J Med Sci 1893;106(2):153–7.
25. Yan C, Zhou JL, Wu JH, Zhang JZ. Case Report Synchronous Granulocytic Sarcoma of the Breast and Spine: A Case Report and Review of the Literature. Vol 121.; 2008.
26. Gomaa W GAEEBKGA. Primary myeloid sarcoma of the breast: a case report and review of literature. J Microsc Ultrastruct 2018;6(4):212–4.
27. Shallis RM, Gale RP, Lazarus HM, et al. Myeloid sarcoma, chloroma, or extramedullary acute myeloid leukemia tumor: A tale of misnomers, controversy and the unresolved. Blood Rev. 2021;47. doi:10.1016/j.blre.2020.100773
28. Yui J MMPMGNAKAEM et al. Myeloid sarcoma: the Mayo Clinic experience of ninety six case series. Blood 2016 Dec 2;128(22):2798.
29. Sharma A, Das AKr, Pal S, Bhattacharyya S. Fine-needle aspiration cytology of granulocytic sarcoma presenting as a breast lump – Report of a rare case with a comprehensive literature search. J Lab Physicians. 2018;10(01):113-115. doi:10.4103/jlp. jlp_114_17
30. Jelić-Puškarić B OKSPAOKDKSIJB. Myeloid sarcoma involving the breast. Coll Antropol 2010;34(2):641-4.
31. Zhang XH ZRLY. Granulocytic sarcoma of abdomen in acute myeloid leukemia patient with inv(16) and t(6;17) abnormal chromosome: case report and review of literature. Leuk Res 2010;34(7):958–61.
32. Ganzel C, Lee JW, Fernandez HF, et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021;5(22):4560-4568. doi:10.1182/bloodadvances.2021004999
33. Heuser M, Ofran Y, Boissel N, et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Annals of Oncology. 2020;31(6):697-712. doi:10.1016/j.annonc.2020.02.018
34. Cunningham I, Kohno B. 18FDG-PET/CT: 21st century approach to leukemic tumors in 124 cases. Am J Hematol. 2016;91(4):379-384. doi:10.1002/ajh.24287
35. Grunwald MR, Levis MJ. FLT3 tyrosine kinase inhibition as a paradigm for targeted drug development in acute myeloid leukemia. Semin Hematol. 2015;52(3): 193-199. doi:10.1053/j.seminhematol.2015.03.004
36. Urbino I, Secreto C, Olivi M, et al. Evolving therapeutic approaches for older patients with acute myeloid leukemia in 2021. Cancers (Basel). 2021;13(20). doi:10.3390/cancers13205075
37. Francesco Angotzi EBCSMBGGM et al. 1523 Disease Course and Treatment Patterns of Acute Myeloid Leukemia with FLT3 Mutations and Myeloid Sarcoma Reveal High Efficacy of Gilteritinib: A Multicentric Retrospective Study. ASH oral and poster abstract