The phase 3 ADMIRAL trial found that patients with relapsed/refractory FLT3-mutation–positive acute myeloid leukemia (AML) who were randomized 2:1 to receive the oral FMS-like tyrosine kinase 3 inhibitor gilteritinib versus those randomized to salvage chemotherapy (SC) had better overall survival. 

Researchers provide a 2-year follow-up of the ADMIRAL study to clarify the long-term therapeutic effects and safety of gilteritinib in these patients with AML. The median surviving follow-up was 37.1 months at the time of the study, with deaths in 203 of 247 and 97 of 124 patients in the gilteritinib and SC arms, respectively; 16 gilteritinib-treated patients stayed on therapy. 

The median overall survival in the gilteritinib and SC groups was 9.3 and 5.6 months, respectively (hazard ratio, 0.665; 95% CI, 0.518, 0.853; two-sided P=.0013); ≥2-year projected survival rates were 20.6% (95% CI, 15.8, 26.0) and 14.2%, respectively (95% CI, 8.3, 21.6). The cumulative recurrence rate after composite complete remission in the gilteritinib arm was 75.7% after two years, with few relapses occurring after 18 months. Overall, 49 of 247 patients in the gilteritinib arm and 14 of 124 patients in the SC arm survived for at least two years. About 26 gilteritinib-treated patients survived for two years without recurrence; 18 of these patients had transplantation (hematopoietic stem cell transplantation [HSCT]), and 16 were resumed on gilteritinib as post-HSCT maintenance treatment. 

Increased liver transaminase levels were the most prevalent adverse events of interest throughout years 1 and 2 of gilteritinib treatment; adverse event frequency was reduced in year 2. As a result, continuous and post-HSCT gilteritinib maintenance medication maintained remission while maintaining a steady safety profile. The data demonstrated that extended gilteritinib treatment was safe and was linked with better survival as compared to SC.