Contributions
Abstract: EP438
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
The phase 3 ADMIRAL trial demonstrated the superiority of gilteritinib to salvage chemotherapy (SC) in patients with FLT3-mutated (FLT3mut+) relapsed or refractory (R/R) acute myeloid leukemia (AML).
Aims
A follow-up of ADMIRAL assessed long-term survivors, hematopoietic stem cell transplantation (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, patients who underwent HSCT, and adverse events (AEs) of interest in Years 1 (≤12 months) and 2 (>12 months) of gilteritinib therapy were evaluated.
Results
As of September 20, 2020, 17% (n=63/371) of patients in the intention-to-treat (ITT) population were alive (gilteritinib, n=49; SC, n=14); 16 patients assigned to gilteritinib remained on treatment. After a median follow-up of 37.1 months, 26 of the 49 patients in the gilteritinib arm who were alive were also without relapse; 18 of these 26 patients underwent HSCT, with 16 receiving post-HSCT gilteritinib maintenance therapy. Nineteen of the 26 patients in the gilteritinib arm without relapse continued gilteritinib beyond 1 year and remained in complete remission (CR).
Of the 371 patients in the ITT population, 83 (22%) underwent HSCT during the study (gilteritinib, n=64; SC, n=19). Pre-HSCT composite CR (CRc) rates were similar across arms (gilteritinib: n=40/64; 63%; SC: n=11/19; 58%); 10 of 11 patients preselected for low-intensity SC achieved pre-HSCT CRc (i.e., the sum of patients who achieved CR with or without complete hematologic or platelet recovery) (gilteritinib, n=9; SC, n=1). Forty of 64 (63%) transplanted patients in the gilteritinib arm received post-HSCT gilteritinib maintenance after achieving pre-HSCT CRc; the 24-month relapse rate in patients who resumed gilteritinib after pre-HSCT CRc was 19%. Post-HSCT treatment with chemotherapy or other tyrosine kinase inhibitors was administered in 26 patients who received gilteritinib before transplantation.
Cumulative 24-month relapse rates in gilteritinib-treated patients who achieved pre-HSCT CR and CRc were 20% and 45%, respectively. Median post-HSCT overall survival (landmarked to the date of HSCT) was similar across arms (gilteritinib, 16.1 months; SC, 15.3 months; HR=1.076; 95% CI: 0.536, 2.160).
Overall, 10.2% of patients (n=25/246) had ≥24 months of gilteritinib exposure. The most common AEs of interest during Years 1 and 2 of gilteritinib therapy were elevated alanine or aspartate aminotransferase levels. Incidences of all AEs of interest declined in Year 2. Cardiac AEs of interest 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.
Conclusion
A high proportion of gilteritinib-treated R/R FLT3mut+ AML patients who were alive without relapse had received HSCT followed by gilteritinib maintenance. Among all transplanted patients 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.
Keyword(s): Flt3 inhibitor
Abstract: EP438
Type: E-Poster Presentation
Session title: Acute myeloid leukemia - Clinical
Background
The phase 3 ADMIRAL trial demonstrated the superiority of gilteritinib to salvage chemotherapy (SC) in patients with FLT3-mutated (FLT3mut+) relapsed or refractory (R/R) acute myeloid leukemia (AML).
Aims
A follow-up of ADMIRAL assessed long-term survivors, hematopoietic stem cell transplantation (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, patients who underwent HSCT, and adverse events (AEs) of interest in Years 1 (≤12 months) and 2 (>12 months) of gilteritinib therapy were evaluated.
Results
As of September 20, 2020, 17% (n=63/371) of patients in the intention-to-treat (ITT) population were alive (gilteritinib, n=49; SC, n=14); 16 patients assigned to gilteritinib remained on treatment. After a median follow-up of 37.1 months, 26 of the 49 patients in the gilteritinib arm who were alive were also without relapse; 18 of these 26 patients underwent HSCT, with 16 receiving post-HSCT gilteritinib maintenance therapy. Nineteen of the 26 patients in the gilteritinib arm without relapse continued gilteritinib beyond 1 year and remained in complete remission (CR).
Of the 371 patients in the ITT population, 83 (22%) underwent HSCT during the study (gilteritinib, n=64; SC, n=19). Pre-HSCT composite CR (CRc) rates were similar across arms (gilteritinib: n=40/64; 63%; SC: n=11/19; 58%); 10 of 11 patients preselected for low-intensity SC achieved pre-HSCT CRc (i.e., the sum of patients who achieved CR with or without complete hematologic or platelet recovery) (gilteritinib, n=9; SC, n=1). Forty of 64 (63%) transplanted patients in the gilteritinib arm received post-HSCT gilteritinib maintenance after achieving pre-HSCT CRc; the 24-month relapse rate in patients who resumed gilteritinib after pre-HSCT CRc was 19%. Post-HSCT treatment with chemotherapy or other tyrosine kinase inhibitors was administered in 26 patients who received gilteritinib before transplantation.
Cumulative 24-month relapse rates in gilteritinib-treated patients who achieved pre-HSCT CR and CRc were 20% and 45%, respectively. Median post-HSCT overall survival (landmarked to the date of HSCT) was similar across arms (gilteritinib, 16.1 months; SC, 15.3 months; HR=1.076; 95% CI: 0.536, 2.160).
Overall, 10.2% of patients (n=25/246) had ≥24 months of gilteritinib exposure. The most common AEs of interest during Years 1 and 2 of gilteritinib therapy were elevated alanine or aspartate aminotransferase levels. Incidences of all AEs of interest declined in Year 2. Cardiac AEs of interest 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.
Conclusion
A high proportion of gilteritinib-treated R/R FLT3mut+ AML patients who were alive without relapse had received HSCT followed by gilteritinib maintenance. Among all transplanted patients 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.
Keyword(s): Flt3 inhibitor