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Randomized Controlled Trial
. 2022 Jun 9;139(23):3366-3375.
doi: 10.1182/blood.2021011583.

Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial

Alexander E Perl  1 , Richard A Larson  2 , Nikolai A Podoltsev  3 , Stephen Strickland  4 , Eunice S Wang  5 , Ehab Atallah  6 , Gary J Schiller  7 , Giovanni Martinelli  8 , Andreas Neubauer  9 , Jorge Sierra  10 , Pau Montesinos  11 , Christian Récher  12 , Sung-Soo Yoon  13 , Naoko Hosono  14 , Masahiro Onozawa  15 , Shigeru Chiba  16 , Hee-Je Kim  17 , Nahla Hasabou  18 , Qiaoyang Lu  18 , Ramon Tiu  18 , Mark J Levis  19
Affiliations
Randomized Controlled Trial

Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial

Alexander E Perl et al. Blood. .

Abstract

The phase 3 ADMIRAL (NCT02421939; Study ID: 2215-CL-0301) trial showed superior overall survival in 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 vs those randomized to receive salvage chemotherapy (SC). Here we provide a follow-up of the ADMIRAL trial 2 years after the primary analysis to clarify the long-term treatment effects and safety of gilteritinib in these patients with AML. At the time of this analysis, the median survival follow-up was 37.1 months, with deaths in 203 of 247 and 97 of 124 patients in the gilteritinib and SC arms, respectively; 16 gilteritinib-treated patients remained on treatment. The median overall survival for the gilteritinib and SC arms was 9.3 and 5.6 months, respectively (hazard ratio, 0.665; 95% confidence interval [CI], 0.518, 0.853; two-sided P = .0013); 2-year estimated survival rates were 20.6% (95% CI, 15.8, 26.0) and 14.2% (95% CI, 8.3, 21.6). The gilteritinib-arm 2-year cumulative incidence of relapse after composite complete remission was 75.7%, 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 were alive for ≥2 years. Twenty-six gilteritinib-treated patients remained alive for ≥2 years without relapse; 18 of these patients underwent transplantation (hematopoietic stem cell transplantation [HSCT]) and 16 restarted gilteritinib as post-HSCT maintenance therapy. The most common adverse events of interest during years 1 and 2 of gilteritinib therapy were increased liver transaminase levels; adverse event incidence decreased in year 2. Thus, continued and post-HSCT gilteritinib maintenance treatment sustained remission with a stable safety profile. These findings confirm that prolonged gilteritinib therapy is safe and is associated with superior survival vs SC. This trial was registered at www.clinicaltrials.gov as #NCT02421939.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient disposition. (A) Disposition according to treatment received. (B) Disposition according to transplantation status: patients remaining alive for ≥2 years without relapse in the gilteritinib arm. (C) Disposition by preselected chemotherapy: patients remaining alive for ≥2 years without relapse in the gilteritinib arm. Due to limited follow-up of patients in the SC arm, data related to posttransplant relapse and survival were not available. ITT, intention-to-treat.
Figure 1.
Figure 1.
Patient disposition. (A) Disposition according to treatment received. (B) Disposition according to transplantation status: patients remaining alive for ≥2 years without relapse in the gilteritinib arm. (C) Disposition by preselected chemotherapy: patients remaining alive for ≥2 years without relapse in the gilteritinib arm. Due to limited follow-up of patients in the SC arm, data related to posttransplant relapse and survival were not available. ITT, intention-to-treat.
Figure 2.
Figure 2.
OS in patients with R/R FLT3+ AML (intention-to-treat population).
Figure 3.
Figure 3.
Cumulative incidence of relapse in patients with R/R FLT3+ AML in the gilteritinib arm. (A) Cumulative incidence of relapse after CR. (B) Cumulative incidence of relapse after CRc.
Figure 4.
Figure 4.
AEs of interest during and after the first year of gilteritinib therapy in patients with R/R FLT3+ AML.
See this image and copyright information in PMC

References

    1. Perl AE, Martinelli G, Cortes JE, et al. . Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019;381(18):1728-1740. - PubMed
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