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

Monica Bocchia,1 Angelo Michele Carella,2 Antonino Mulè,3 Lorenzo Rizzo,4 Mauro Turrini,5 Maria Chiara Abbenante,2 Roberto Cairoli,4 Valeria Calafiore,3 Marzia Defina,1 Angelo Gardellini,5 Giovanni Luzi,6 Caterina Patti,3 Maria Beatrice Pinazzi,6 Marta Riva,4 Giovanni Rossi,2 Vincenzo Sammartano,1 Luigi Rigacci6 1Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy; 2Division of Hematology with Hematologic Intensive Care Unit and Cellular Therapies, Department of Medical Science, Fondazione IRCCS Casa Sollievo Della Sofferenza, Foggia, Italy; 3UOC Hematology and Oncology, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy; 4Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 5Division of Hematology, Valduce Hospital, Como, Italy; 6UOC Hematology and Stem Cell Transplant Unit, Ospedale S, Camillo, Rome, ItalyCorrespondence: Angelo Michele Carella, Division of Hematology with Hematologic Intensive Care Unit and Cellular Therapies, Department of Medical Science, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo, Foggia, 71013, Italy, Tel +390882410054, Fax +390882410322, Email am.carella@operapadrepio.itAbstract: 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.Keywords: acute myeloid leukemia, FLT3, midostaurin, gilteritinib