KEY TAKEAWAYS
- Phase 3 ADMIRAL trial showed superior survival in relapsed/refractory FLT3-mutation-positive AML patients with gilteritinib vs. salvage chemotherapy.
- The study’s primary aim was to evaluate the long-term treatment effects and safety of gilteritinib in these patients with AML.
- The method used in the study was a randomized controlled trial with a 2:1 ratio of gilteritinib vs. salvage chemotherapy.
- The study’s outcome showed that gilteritinib therapy was safe and associated with superior survival compared to salvage chemotherapy with continued and post-HSCT gilteritinib.
Patients with relapsed/refractory FLT3-mutation-positive acute myeloid leukemia (AML) randomized 2:1 to receive the oral FMS-like tyrosine kinase 3 inhibitor gilteritinib compared favorably with those randomized to receive salvage chemotherapy (SC) in the phase 3 ADMIRAL (NCT02421939; Study ID: 2215-CL-0301) trial. To further understand the long-term therapy effects and safety of gilteritinib in these patients with AML, we present a follow-up of the ADMIRAL trial 2 years after the primary analysis. There were 203 deaths among 247 patients who received gilteritinib and 97 deaths among 124 patients who received SC at this analysis, with 16 patients receiving gilteritinib still receiving treatment. Two-year estimated survival rates were 20.6% (95% CI, 15.8, 26.0) and 14.2% (95% CI, 8.3, 21.6) for the gilteritinib and SC groups, respectively (hazard ratio, 0.665; 95% CI, 0.518, 0.853; two-sided P =.0013).
Few relapses occurred after 18 months in the gilteritinib arm, with a 2-year cumulative incidence of recurrence following composite complete remission of 75.7%. There were 49 survivors out of 247 in the gilteritinib group and 14 survivors out of 124 in the SC group after 2 years. About 26 patients treated with gilteritinib for at least two years without relapse are still alive today; eighteen underwent transplantation (hematopoietic stem cell transplantation [HSCT]), and sixteen resumed gilteritinib as a post-HSCT maintenance medication. The incidence of adverse events decreased in 2 years of gilteritinib therapy, with elevated liver transaminase levels being the most common adverse event of interest in both years 1 and 2. Thus, remission was maintained with a steady safety profile while receiving ongoing and post-HSCT gilteritinib maintenance medication. These results demonstrate the safety of long-term gilteritinib treatment and its correlation with improved survival compared to SC.
Source: https://pubmed.ncbi.nlm.nih.gov/35081255/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02997202
Perl AE, Larson RA, Podoltsev NA, Strickland S, Wang ES, Atallah E, Schiller GJ, Martinelli G, Neubauer A, Sierra J, Montesinos P, Récher C, Yoon SS, Hosono N, Onozawa M, Chiba S, Kim HJ, Hasabou N, Lu Q, Tiu R, Levis MJ. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022 Jun 9;139(23):3366-3375. doi 10.1182/blood.2021011583. PMID: 35081255; PMCID: PMC9197557.
