Abstract
A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with standard therapy was particularly low. We retrospectively assessed the characteristics and outcome of patients with R/R FLT3-mutated AML included in the Toulouse–Bordeaux DATAML registry. Among 347 patients who received FLT3 TKI-free intensive chemotherapy as first-line treatment, 174 patients were refractory (n = 48, 27.6%) or relapsed (n = 126, 72.4%). Salvage treatments consisted of intensive chemotherapy (n = 99, 56.9%), azacitidine or low-dose cytarabine (n = 9, 5.1%), other low-intensity treatments (n = 17, 9.8%), immediate allogeneic stem cell transplantation (n = 4, 2.3%) or best supportive care only (n = 45, 25.9%). Among the 114 patients who previously received FLT3 TKI-free intensive chemotherapy as first-line treatment (refractory, n = 32, 28.1%; relapsed, n = 82, 71.9%), the rate of CR (complete remission) or CRi (complete remission with incomplete hematologic recovery) after high- or low-intensity salvage treatment was 50.0%, with a bridge to transplant in 34.2% (n = 39) of cases. The median overall survival (OS) was 8.2 months (interquartile range, 3.0–32); 1-, 3- and 5-year OS rates were 36.0% (95%CI: 27–45), 24.7% (95%CI: 1–33) and 19.7% (95%CI: 1–28), respectively. In this real-word study, although response rate appeared higher than the controlled arm of the ADMIRAL trial, the outcome of patients with R/R FLT3-mutated AML remains very poor with standard salvage therapy.
Highlights
FMS-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase expressed in early hematopoietic stem and progenitor cells that regulates their proliferation and differentiation [1]
Out of 3290 newly diagnosed acute myeloid leukemia (AML) patients included in the DATAML registry between 2000 and 2017, 1453 did not have a recorded status for FLT3 mutation and 364 were not selected to receive intensive chemotherapy as a first-line treatment
Most AML patients refractory to standard induction chemotherapy or relapsing after complete response die from disease progression
Summary
FMS-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase expressed in early hematopoietic stem and progenitor cells that regulates their proliferation and differentiation [1]. The ADMIRAL phase 3 trial, designed for relapsed/refractory (R/R) FLT3-mutated AML patients, recently demonstrated the superiority of gilteritinib as single agent over the control treatment arm [8], which was determined by investigators prior to 2:1 randomization between mitoxantrone, etoposide, cytarabine (MEC), fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin (FLAG-IDA), azacitidine (AZA) or low-dose cytarabine (LDAC). These regimens are recognized as acceptable salvage regimens in this situation, other combinations based on intermediate- or high-dose cytarabine or even single-agent cytarabine are widely used [11]. In the ADMIRAL trial, overall survival (OS) was significantly improved in the gilteritinib arm compared to the control arm with a hazard ratio (HR) of 0.64
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