P056 | A META-ANALYSIS ON GILTERITINIB USING REAL-WORLD AND RANDOMIZED TRIAL DATA IN PATIENTS WITH FLT3-MUTATED REFRACTORY/RELAPSED ACUTE MYELOID LEUKEMIA.

The second-generation tyrosine kinase inhibitor (TKI) gilteritinib has demonstrated significant efficacy for pts with relapsed or refractory (r/r) FLT3mut + AML, including FLT3-TKD and FLT3-ITD subtypes. This study included pts from both clinical trials (RCT) and real-world evidence studies (RWE) and employed a meta-analytic approach to evaluate the efficacy of gilteritinib in a composite patient cohort. A random-effects model was utilized to extract and synthesize the efficacy endpoints, including OS, ORR, and CR to ensure consistency in analysis. The χ2Q test and I2 statistics were used to evaluate the heterogeneity of the data. P<0.05 indicated significant heterogeneity for the Q test, while I2 value >50% indicated significant heterogeneity for the I2 statistics. A total of 829 pts with AML were included in the six studies analyzed. A pooled analysis combining both RCT and RWE data revealed an 85% (95% CI 75%–92%) prevalence of the FLT3-ITD mutation, with substantial heterogeneity across studies (Q = 54.94, I2 = 91%, p = 0.00). In contrast, 14% of cases (95% CI 10–17%) had the FLT3-TKD mutation, with a more homogeneous distribution across RCT and RWE pts (Q = 10.44, I2 = 0%, p = 0.06). The cCR rate in the pooled analysis demonstrated significant heterogeneity (Q = 57.72, p = 0.00, I2 = 91%) and was 43% (95% CI 32–56%) (Figure 1A). Approximately 29% of pts (95% CI 13–48%) had received prior FLT3-targeted therapy, with considerable variation across study populations (Q = 96.16, p = 0.00, I2 = 96%). Despite these differences in FLT3-ITD prevalence, cCR rates and prior FLT3-targeted therapy between RCT and RWE the OS rate remained consistent. The 1-year OS rate was 36% (95% CI 33–39%), with no significant variation across studies (Q = 1.95, p = 0.86, I2 = 0%) (Figure 1C). Of note, gilteritinib served as a bridge to allogeneic bone marrow transplantation (BMT) in 23% of patients (95% CI, 20–26%), with a consistent distribution across RCT and RWE settings (Q = 6.04, p = 0.30, I2 = 17%) (Figure 1B). Our meta-analysis, which includes patients who had not been previously exposed to FLT3 inhibitors, as well as patients who had received induction therapies incorporating these agents, suggests a general improvement in OS. The 1-year OS rate remained consistent at 36%, with no significant heterogeneity across the studies. Access to BMT enhanced by gilteritinib in about one-quarter of r/r AML patients highlighting its potential as a curative strategy whatever the care setting.