Improvement in clinical outcome of FLT3 ITD mutated acute myeloid leukemia patients over the last one and a half decade

Abstract

AML with FLT3 ITD mutations are associated with poor outcome. We reviewed outcomes of patients with FLT3 ITD mutated AML to investigate trends over time. We analyzed 224 AML patients (excluding patients with core binding factor and acute promyelocytic leukemia) referred to our institution between 2000 and 2014. Patients were divided into five cohorts by era: 2000-2002 (Era 1, n=19), 2003-2005 (Era 2, n=41), 2006-2008 (Era 3, n=53), 2009-2011 (Era 4, n=55), and 2012-2014 (Era 5, n=56) to analyze differences in outcome. The baseline characteristics were not statistically different across Eras. The response rate (CR/CRp) from Era 1-5 was 68%, 49%, 72%, 73%, and 75%, respectively. The overall response rate (all Eras) with chemotherapy alone versus chemotherapy plus FLT3 inhibitor was 67% and 72.5%, respectively (P=0.4). The median time to relapse was 6, 3.6, 7.9, 8.1 months and not reached from Eras 1 through 5, respectively (P=0.001). The median OS has improved: 9.6, 7.6, 14.4, 15.7, and 17.8 month from Eras 1-5, respectively (P=<0.001). Stem cell transplant as a time-dependent variable, showed better OS in the univariate analysis (HR: 0.57, 95% CI: 0.39-0.84, P=0.004) but did not retained its significance in multivariate analysis (HR: 0.75, 95% CI: 0.50-1.13, P=0.16). Our data suggest improvement in outcome of FLT3 ITD mutated AML patients over the last 15 years. This is probably due to improvement in treatment strategies, including but not limited to integration of FLT3 inhibitors and increased use of SCT.