Tyrosine kinase inhibitors for acute myeloid leukemia: A step toward disease control?

Autores de IIS La Fe

• Juan Eduardo Megías Vericat

  Autor

• Octavio Antonio Ballesta López

  Autor

• Eva Barragán González

  Autor

• David Martínez Cuadrón

  Autor

• Pau Montesinos Fernández

  Autor

Grupos

• Farmacogenética

• Hematología y Hemoterapia

Abstract

Dysregulation of tyrosine kinases (TKs) may play a role in leukemogenesis by promoting survival and proliferation of acute myeloid leukemia (AML) cells. In AML, the main TKs mutations are produced in Fms-like tyrosine kinase 3 (FLT3), KIT and Janus kinase (JAK) genes, and with less frequency in BCR-ABL. The striking results with TK Inhibitors (TKIs) therapy in BCR-ABL1 chronic myeloid leukemias has paved the way for its clinical development in AML. However, the AML biology complexity seems to prevent TKI therapy from being proposed as a strong shift in the treatment paradigm and prognosis. While some FLT3 inhibitors have shown efficacy in well-designed studies, an increasing number of AML patients are being treated with TKIs as a new standard of care, compassionate use, or in clinical trials. We will review the current clinical evidence concerning the use of TKIs in different subsets of AML (BCR-ABL1, Core Binding Factor, FLT3 mutated, and FLT3 wild-type) to address the main topics concerning these targeted therapies for AML: 1) optimal place (upfront, relapsed/refractory or maintenance); 2) monotherapy or combination; 3) efficacy in TK mutated versus wild-type patients; 4) differences between selective and multi-targeted TKIs. In the next years, clinical trials and real-world data will help answer these questions and establish the impact of TKIs on outcomes of AML patients. © 2020 Elsevier Ltd

Keywords

• Animals; Antineoplastic Agents; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Mutation; Protein Kinase Inhibitors; azacitidine; bemcentinib; cabozantinib; CD135 antigen; cediranib; core binding factor; crenolanib; cyclosporine; CYP3A4 inhibitor; cytarabine; dasatinib; daunorubicin; entospletinib; ff 10101; gilteritinib; granulocyte colony stimulating factor; ibrutinib; idarubicin; imatinib; ketoconazole; lestaurtinib; midostaurin; mivavotinib; nilotinib; oxygenase inhibitor; pacritinib; pantoprazole; phenytoin; placebo; ponatinib; protein tyrosine kinase inhibitor; quizartinib; rifampicin; ruxolitinib; sar 103168; sel24 b489; semaxanib; sorafenib; sunitinib; unclassified drug; antineoplastic agent; CD135 antigen; FLT3 protein, human; protein kinase inhibitor; acute kidney failure; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; anemia; anorexia; antineoplastic activity; bleeding; bone marrow suppression; bone pain;