Hematologists Demonstrate Sub-Optimal Knowledge of FLT3 Mutations in Acute Myeloid Leukemia
Authors: Willis Lauren , Fagerlie Sara R. 
Published: October 2019

Abstract
Background: The objective of this study was to assess current clinical practices of hematologist/oncologist (hem/onc) specialists related to FLT3 mutations and FLT3 inhibitors used in acute myeloid leukemia (AML), in order to identify knowledge, competency, and practice gaps and barriers to optimal care.
Methods: A continuing medical education (CME)-certified clinical practice assessment consisting of 25 multiple choice questions that were designed to measure knowledge, skills, attitudes, and competence of hem/onc specialists regarding FLT3 mutations and FLT3 inhibitors used in AML. The survey instrument was made available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. The activity launched on March 26, 2018, and participant responses are still being collected at the time of abstract submission.
Results: At the time of this report there are 122 hem/onc activity participants, collection is on-going. Demographics and treatment practices are listed in Table 1, and levels of confidence and barriers to incorporating mutation testing are listed in Table 2.FLT3 Mutations and Testing RecommendationsThe assessment demonstrated there are low levels of knowledge about prevalence, prognostic significance of, and optimal testing methods for FLT3 mutations in AML.Despite a majority (84%) demonstrating knowledge that FLT3-ITD mutational analysis is strongly recommended (per CAP/ASH guidelines) in all patients at initial workup, only 38% indicated they test 100% of their newly diagnosed AML patients for FLT3 mutations74% could not identify the prevalence of activating FLT3 mutations in adults with AML, and 44% could not identify the prognostic significance of FLT3-ITD and FLT3-TKD mutations in AML94% could not identify the optimal method to determine FLT3 mutation status in newly diagnosed AMLClinical Trial Data and Assessing Treatment ResponseRevealed relatively low levels of knowledge of clinical trial data with FLT3 inhibitors and the appropriate time to assess response to treatment.61% were unable to identify efficacy outcomes from the midostaurin phase 3 RATIFY trial60% were unable to recognize the optimal time to obtain a bone marrow aspiration and biopsy after initiating cycle 1 of induction therapy in a patient that received midostaurinTreatment Related Adverse Events and Administration ConsiderationsLess than optimal awareness of adverse events and drug-drug interactions that can occur with FLT3 inhibitors.47% were unaware that posaconazole can interact with midostaurin leading to increased serum midostaurin levels73% did not recognize the need to hold midostaurin if a patient develops grade 3-4 pulmonary infiltrates, based on the RATIFY trial protocolNovel FLT3 InhibitorsRevealed a very low level of knowledge about second generation FLT3 inhibitors regarding additional targets other than FLT3 and activity against specific FLT3 mutations.96% could not recognize additional targets of novel FLT3 inhibitors79% could not recognize which form of FLT3 mutations (ITD or TKD) novel inhibitors targeted
Conclusions: After decades of using the same initial treatment for AML, key advances have led to therapy changes for subsets of patients with AML such as those with FLT3 mutations. Gaps in clinical knowledge and competence for hem/onc practitioners were identified in this assessment.These deficiencies included testing for FLT3 mutations and integrating FLT3 inhibitors into therapy for the treatment of patients with AML. Additionally, the activity demonstrated gaps in the knowledge of testing recommendations and the practice of FLT3 mutation testing in all newly diagnosed AML patients. Additional education is needed to improve the knowledge, competence, and confidence of academic and community hem/onc specialists who care for patients with AML.

Disclosures
No relevant conflicts of interest to declare.