The Ever-Changing Therapeutic Landscape of AML: A Real World Experience of Novel Therapies on Outcomes

After many decades of stagnation, several promising novel therapies have recently been approved for the management of patients (pts) with Acute Myeloid Leukemia (AML). Many of these target pts in specific clinical and molecular subsets such as midostaurin/gilteritinib for FLT3-mutated AML, liposomal daunorubicin-cytarabine for secondary AML, and fractionated gemtuzumab ozogamicin (GO) for good risk AML. To address the dismal outlook for elderly AML patients, we now have venetoclax or glasdegib combinations. Single agent FLT3 inhibitors (resulting in ~4 m improvement in overall survival (OS)) and IDH inhibitors (response rate 40%, doubled OS in responders) have shown to be superior to traditional approaches in the relapsed setting. Although these agents are exciting, a majority of pts with AML present with intermediate and high-risk disease and only a small subset will have actionable mutations. In order to determine the impact of these newer therapies on outcome for our pts, we investigated AML outcomes for pts diagnosed and treated since 2017 and compared these with survival for similar pts treated in the prior two years (y). We performed a retrospective chart review to identify newly diagnosed pts treated with chemotherapy over a 2y period (2015-17) prior to the first FDA approval of Midostaurin in April, 2017 (old AML era or group 1) and the 2y since approval (2017-19; new AML era or group 2). We reviewed charts of 138 AML pts meeting these criteria at our institution: 79 in group 1 and 59 in group 2. Demographics, disease-specific variables, as well as outcomes of interest (overall survival (OS), overall response rate (CR/CRi)) were collected on an IRB-approved protocol. Responses were defined according to the 2003 International Working Group (IWG) criteria. Demographics, baseline characteristics, and treatment responses were analyzed using descriptive statistics. Overall survival was estimated utilizing Kaplan-Meier (KM) survival analysis. Clinical characteristics were comparable in both groups. Median age was 65y with slight differences in gender distribution (Table 1). ELN risk categories (Döhner, Blood. 2017) across the groups were similarly distributed; a majority of pts had intermediate and adverse risk characteristics. As expected, more pts received newer therapies in group 2. 6 pts (7.6%) in group 1 received new drugs (as part of clinical trials), while 31 (52%) received newer therapies in group 2. Newer therapies were mostly GO (28%), midostau