Follow-up of patients with <i>FLT3-</i>mutated R/R AML in the phase 3 ADMIRAL trial.
Authors: Alexander E. Perl, Richard A. Larson, Nikolai Alexandrovich Podoltsev, Stephen Strickland, Eunice S. Wang, Gary J. Schiller, Giovanni Martinelli, Andreas Neubauer, Jorge Sierra, Pau Montesinos, Christian Recher, Sung-Soo Yoon, Naoko Hosono, Masahiro Onozawa, Shigeru Chiba, Hee-Je Kim, Nahla Hasabou, Qiaoyang Lu, Ramon Velasquez Tiu, Mark J. Levis
Journal: Journal of Clinical Oncology (2021)

7013 Background: The phase 3 ADMIRAL trial demonstrated the superiority of gilteritinib to salvage chemotherapy (SC) in patients (pts) with FLT3-mutated ( FLT3 mut+ ) R/R AML. Aim/Objective: A follow-up of ADMIRAL assessed long-term survivors, transplant (HSCT) outcomes. and gilteritinib safety beyond 1 year. Methods: A data cut was performed on September 20, 2020—2 years after the primary analysis. Patients who were alive without relapse, pts who underwent HSCT, and adverse events of interest (AEIs) in Years 1 (≤12 months) and 2 ( &gt; 12 months) of gilteritinib therapy were evaluated. Results: As of September 20, 2020, 17% (n = 63/371) of pts in the intention-to-treat (ITT) population were alive (gilteritinib, n = 49; SC, n = 14); 16 pts assigned to gilteritinib remained on treatment. After a median follow-up of 37.1 months, 26 of the 49 pts in the gilteritinib arm who were alive were also without relapse; 18 of these 26 pts underwent HSCT, with 16 receiving post-HSCT gilteritinib maintenance therapy. Nineteen of the 26 pts in the gilteritinib arm without relapse continued gilteritinib beyond 1 year and remained in CR. Of the 371 ITT pts, 83 (22%) underwent HSCT during the study (gilteritinib, n = 64; SC, n = 19). Pre-HSCT CRc rates were similar across arms (gilteritinib: n = 40/64; 63%; SC: n = 11/19; 58%); 10 of 11 pts preselected for low-intensity SC achieved pre-HSCT CRc (gilteritinib, n = 9; SC, n = 1). Forty of 64 (63%) transplanted pts in the gilteritinib arm received post-HSCT gilteritinib maintenance after achieving pre-HSCT CRc; the 24-month relapse rate in pts who resumed gilteritinib after pre-HSCT CRc was 19%. Post-HSCT treatment with chemotherapy or other tyrosine kinase inhibitors was administered in 26 pts who received gilteritinib before transplantation. Cumulative 24-month relapse rates in gilteritinib-treated pts who achieved pre-HSCT CR and CRc were 20% and 45%, respectively. Median post-HSCT overall survival (landmarked to HSCT date), was similar across arms (gilteritinib, 16.1 months; SC, 15.3 months; HR = 1.076; 95% CI: 0.536, 2.160). Overall, 10.2% (n = 25/246) had ≥24 months of gilteritinib exposure. Most common AEIs during Years 1 and 2 of gilteritinib therapy were elevated ALT/AST levels. Incidences of all AEIs declined in Year 2. Cardiac AEIs in Year 2 were nonfatal cardiorespiratory arrest (n = 1) and ventricular tachycardia (n = 1). One case of differentiation syndrome and cutaneous squamous cell carcinoma occurred in Years 1 and 2, respectively. Conclusions: A high proportion of gilteritinib-treated R/R FLT3 mut+ AML pts who were alive without relapse had received HSCT followed by gilteritinib maintenance. Among all transplanted pts in ADMIRAL, pre-HSCT remission rates and post-HSCT survival were similar across arms. Post-HSCT gilteritinib maintenance may relate to the low post-HSCT relapse rate in the gilteritinib arm. The safety profile of gilteritinib is stable at 2 years with no new or significant safety signals. Clinical trial information: NCT02421939.