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Acute myeloid leukemia (AML) is a malignant condition of poorly differentiated hematopoietic progenitor cells.1 The disease can manifest in the eye with tissue hemorrhage or infiltration and be the presenting sign of systemic disease or evidence of relapse. Most frequently, leukemic infiltration involves the retina or choroid, whereas iridociliary involvement is rare.2,3 Management of the systemic disease is key to controlling leukemic ophthalmopathy, but often the eye requires additional radiotherapy, especially for optic-nerve involvement.3
Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are vital for cell proliferation and survival in AML.4 Mutations in FLT3 occur as internal tandem duplication (ITD) or tyrosine kinase domain mutations and are present in 25% and 7% to 10% of all individuals with AML, respectively.4 Studies have demonstrated that FLT3-ITD+ AML confers a worse prognosis.4
Gilteritinib hemifumarate (Astellas Pharma), a newer, type 1 tyrosine kinase inhibitor, is efficacious for FLT3+ AML, with higher specificity for FLT3-ITD and tyrosine kinase domain mutations and less toxicity than multitargeted tyrosine kinase inhibitors.4 Mice treated with gilteritinib demonstrated greater FLT3+ AML tumor regression compared with control mice.1 In an open-label, phase 1/2 clinical trial for relapsed or refractory AML, patients treated with at least 80 mg of gilteritinib daily achieved a 52% overall response rate.5 In this report, we present a patient with relapsed FLT3-ITD+ AML (iridociliochoroidal myeloid sarcoma) responsive to gilteritinib.5
Report of a Case
A patient in their 60s with leukemia cutis and a white blood cell count of 5500 cells/μL (normal, 4000-11 000 cells/μL [to convert to ×109 per liter, multiply by 0.001]) was diagnosed with FLT3-ITD+ AML. Treatment included 7 + 3 cytarabine and idarubicin induction therapy (a 7-day course of cytarabine followed by a 3-day course of idarubicin) with complete remission confirmed on a subsequent bone-marrow biopsy. The patient did not receive a midostaurin or allogeneic stem cell transplant, both of which are typically recommended for FLT3-ITD+ AML. One cycle of high-dose cytarabine was administered as a consolidation therapy. A few weeks later, new nodular lesions in the right axilla and scalp were noted. The patient’s white blood cell count was 18 900 cells/μL, and imaging revealed multiple infiltrative joint lesions, consistent with relapsed AML. This was followed by acute-onset photophobia and visual acuity loss, which led to detection of an intraocular mass and a referral for our opinion.
On examination, visual acuity was hand motions OD and 20/25 OS. An ocular examination revealed a yellow-white infiltrative mass in the right eye involving the temporal iris, ciliary body, and choroid, measuring 15 mm in diameter and 11 mm in thickness, with localized dependent hyphema (Figure, A). The left eye was normal. On B-scan ultrasonography and ultrasound biomicroscopy, the tumor was uniformly hyperechoic (Figure, B). Given the systemic relapse of AML, clinical suspicion for ophthalmic myeloid sarcoma was made. The patient deferred fine-needle aspiration biopsy and radiotherapy. Instead, given the FLT3-ITD mutation, the patient began treatment with oral gilteritinib (120 mg daily for 28 days). At follow-up, the tumor had greatly regressed, with complete disappearance of the iris component (Figure, C) and reduction in the ciliochoroidal component to a 4.7-mm thickness (Figure, D). Visual acuity improved to 20/70 OD with no sign of active disease. Unfortunately, the patient died less than a year after presenting to us because of systemic worsening of AML.
A, A patient in their 60s presented with an iridociliochoroidal myeloid sarcoma secondary to relapsed acute myeloid leukemia, located temporally (A) as a yellow-white mass at upper left with hyphema inferiorly. B, B-scan ultrasonography (12 MHz) demonstrating a uniformly hyperechoic mass of 15 mm in basal diameter and 11 mm in thickness. At follow-up after gilteritinib treatment, the iris mass has completely resolved (C), leaving iris stromal atrophy temporally, and B-scan ultrasonography documented residual thickness of 4.7 mm with no active disease (D).
In a recent phase 3 trial of gilteritinib vs salvage chemotherapy for relapsed/refractory FLT3+ AML, gilteritinib significantly extended median survival compared with salvage chemotherapy (9.3 vs 5.6 months; hazard ratio, 0.637 [95% CI, 0.490-0.830]; P < .001).6 Gilteritinib is now US Food and Drug Administration approved for the treatment of relapsed or refractory AML with FLT3+ mutation. Further investigations on duration and frequency of gilteritinib might aid in understanding its efficacy and safety for ophthalmic FLT3+ AML.
Corresponding Author: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 840 Walnut St, Ste 1440, Philadelphia, PA 19107 (firstname.lastname@example.org).
Published Online: March 12, 2020. doi:10.1001/jamaophthalmol.2020.0110
Conflict of Interest Disclosures: Dr Shields reports receiving support from the Eye Tumor Research Foundation. No other disclosures were reported.
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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. Published online March 12, 2020. doi:10.1001/jamaophthalmol.2020.0110
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