Successful treatment with gilteritinib for isolated extramedullary relapse of acute myeloid leukemia with FLT3-ITD mutation after allogeneic stem cell transplantation

Kida, Michiko; Kuroda, Yuko; Kido, Miki; Chishaki, Ren; Kuraoka, Kazuya; Ito, Takuo

doi:10.1007/s12185-020-02855-4

Cited by 14 publications

(15 citation statements)

References 25 publications

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“…Kanate et al 41 reported findings from a patient with refractory myeloid sarcoma who achieved complete remission with single-agent venetoclax. Kida et al 42 reported the results of HSCT in a patient who had extramedullary relapse myeloid sarcoma with FLT3-ITD mutation and resistance to chemotherapy; monotherapy with gilteritinib (120 mg/d) resulted in complete remission. Furthermore, cytotoxic T lymphocyte–associated protein 4 inhibitors 43 and CD33 monoclonal antibodies 44 have successfully treated myeloid sarcoma.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma

Zhao

Dong

Wan

et al. 2022

Sci Rep

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Myeloid sarcoma is a rare manifestation of acute myeloid leukemia (AML) and is associated with poor overall survival (OS). The optimal treatment remains unclear. The study retrospectively evaluated 118 patients with myeloid sarcoma who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to July 2021. All cases were diagnosed by tissue biopsy. 41 patients underwent genetic mutation analysis. The most frequent genetic mutations were KIT (16.6%), followed by TET2 (14.6%), and NRAS (14.6%). The median survival time of 118 patients was 4 months (range, 1–51 months), while the median survival time of 11 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 19 months (range, 8–51 months). 4 (36.4%) of the 11 patients experienced relapse within 1 year after transplantation. 1 patient died from a severe infection. Of the 6 surviving patients, 5 patients have received maintenance treatment with decitabine after transplantation, and all remained in a state of recurrence-free survival. Patients with myeloid sarcoma have a very unfavorable outcome. Allo-HSCT is an effective treatment option. Recurrence remains the main cause of transplant failure. Maintenance treatment with decitabine after transplantation can prolong the recurrence-free survival time, although these results must be verified in a study with expanded sample size.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma

Zhao

Dong

Wan

et al. 2022

Sci Rep

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“…After 180 days, he has an extensive chronic graft associated to several subcutaneous tumors, diagnosed as myeloid sarcoma and successfully treated with gilteritinib. 25 …”

Section: Discussionmentioning

confidence: 99%

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy

Bocchia¹,

Carella²,

Mulè³

et al. 2022

PGPM

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Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.

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“…In addition, a rare adverse event of gilteritinib, manifesting in 0.6% of treated patients, is posterior reversible encephalopathy syndrome [4], which could represent a possible clue of its penetration into the BBB. We found only limited data about effective treatment with gilteritinib of extramedullary relapses as myeloid sarcoma [15, 16]. In particular, in the case reported by Kim et al [17], a patient with an iridociliochoroidal myeloid sarcoma responded to gilteritinib, a site where drug penetration may be reduced by the presence of the blood-retinal barrier [18].…”

Section: Discussionmentioning

confidence: 99%

A Relapsing Meningeal Acute Myeloid Leukaemia FLT3-ITD+ Responding to Gilteritinib

et al. 2021

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A patient with a therapy-related acute myeloid leukaemia (AML), NPM1<sup>mut</sup>, and FLT3-ITD+ was treated with induction and consolidation with CPX-351, obtaining a complete response (CR) but minimal residual disease persisted positive. Later, she complained progressive burning leg pain, weakening of the right hand and leg muscles, associated with absence of osteotendinous leg reflexes. Examination of cerebrospinal fluid (CSF) showed a meningeal relapse of AML. Moreover, a magnetic resonance imaging (MRI) showed 2 right meningeal implants of myeloid sarcoma and bone marrow revealed haematologic relapse of disease. She was treated with medicated lumbar punctures (LPs) followed by an FLA-Ida scheme, and she achieved a 2nd CR. Unfortunately, the patient developed hyperleucocytosis and reappearance of meningeal myeloid sarcoma at MRI. For this reason, a monotherapy with gilteritinib (an FLT3 inhibitor) was started: after 3 months of therapy, central nervous system (CNS)-disease shrunken and then faded, while AML in the bone marrow achieved only a partial response. This is the 1st report of a positive biological effect of gilteritinib on CNS (meningeal) myeloid sarcoma. There are no studies of gilteritinib concentration into CSF and penetration of gilteritinib into the blood-brain barrier should be further studied, given the paucity of drugs active on CNS relapse of AML. In patients receiving CPX-351 only, diagnostic LP should be considered after induction.

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Successful treatment with gilteritinib for isolated extramedullary relapse of acute myeloid leukemia with FLT3-ITD mutation after allogeneic stem cell transplantation

Cited by 14 publications

References 25 publications

Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma

Clinical characteristics, treatment, and prognosis of 118 cases of myeloid sarcoma

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy

A Relapsing Meningeal Acute Myeloid Leukaemia FLT3-ITD+ Responding to Gilteritinib

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