Pb1858: prognosis and treatment of flt3 mutated myeloid sarcoma in the era of flt3 inhibitors: retrospective evaluation in 5 italian centers.

Topic: 4. Acute myeloid leukemia - Clinical Background: Myeloid sarcoma is a rare neoplastic condition, whose clinical characteristics and optimal treatment are not well defined, especially in relapsed setting. Although FLT3 ITD or TKD mutations have been described in 6-17% of patients, little is known of the activity of FLT3 inhibitors in this setting Aims: The aim of this study is to report clinical characteristics and outcome of myeloid sarcoma associated with FLT3 mutated AML. Methods: We reviewed clinical records of 16 FLT3 mutated patients (5 males and 11 females; median age at diagnosis, 60 years; range, 30-71) with myeloid sarcoma, diagnosed in five Italian centers between 2011 and 2022. Results: At diagnosis median WBC was 86,5x109/L (range 262-3,4);10 (62,5%) patients were FLT3 ITD+, 25% were FLT3 TKD+ and 12,5% were FLT3 wild type. These latter gained FLT3 at first relapse, one ITD and one TKD. Eleven patients (68,8%) co-harbored NPM1 mutation at diagnosis. ELN 2022 risk classification was favorable in 5 (31,3%) patients, intermediate in 9 (56,3%) patients, adverse in 1(12,4%) patient. Myeloid sarcoma was diagnosed in skin (n=9), in CNS (n=5), in lymph nodes (n=2), in colorectal (n=1), in breast (n=1) and ovarian (n=1). In 13 patients (81%) myeloid sarcoma were present at diagnosis, while 3 patients developed it at first relapse of AML. First line therapy was 3 + 7 or analogues in 81,3% of patients, CPX-351 in one patient, HMA plus venetoclax in one patient. Only one patient underwent radiotherapy during induction or salvage chemotherapy. Five (31,3%) patients received midostaurin as part of their induction regimen. Allo-HCT was performed in 6 patients, 3 in first CR and 3 in second CR. Median OS of the entire cohort was 19.9 months. In patients treated with midostaurin as a part of their induction regimen CR rate was 60%, median OS was 18.5 months, and median EFS was 16.7 months. One of these patients was refractory only because of myeloid sarcoma persistence. Nine patients (56%) received gilteritinib at first or subsequent relapses. CR rate was 55.6%. Median number of cycles was 4, and median number of cycles before achieving best response was 2. Notably, two out of the three patients with CNS involvement treated with gilteritinib achieved CR. Extra hematological toxicities were mild (CTCAE 1-2) and only in 2 cases led to dosage reduction. Gilteritinib was bridge to allo-HCT in 22.2% of patients. OS from initiation of gilteritinib was 9.6 months, with 50.5% of patients alive at 12 months. Summary/Conclusion: The prognosis of FLT3 mutated AML with associated myeloid sarcoma remains dismal despite new FLT3 inhibitors. Effectiveness of addition of midostaurin in induction therapy in such rare condition is not defined. Gilteritinib could play a role in relapsed setting, and in our series demonstrated activity in CNS disease; this positive effect needs to be validated in a larger series of patients. Keywords: FLT3, Acute myeloid leukemia