At present, it is not clear whether prophylactic fms-like tyrosine kinase – internal tandem duplication (FLT3-ITD) inhibition with sorafenib, a tyrosine kinase inhibitor, after allogeneic stem cell transplantation (allo-SCT) has any significant impact on relapse and outcomes of patients with FLT3-ITD-positive acute myeloid leukemia (AML) in complete hematological remission (CHR). The phase II SORMAIN trial (EudraCT 2010-018539-16) is a randomized, double-blind, placebo-controlled study, evaluating sorafenib as maintenance therapy after allo-SCT in patients with FLT3-ITD–positive AML. The results of this study were presented by Andreas Burchert from the University of Marburg, Germany, at the 60th American Society of Hematology Annual Meeting & Exposition.
Eighty-three patients (median age = 54.0 years; range, 18.58–75.58) with FLT3-ITD AML who underwent allo-SCT and were in confirmed CHR at the time of screening between day +30 and day +100 post-allo-SCT were included in this study. Patients were randomized to receive sorafenib (n = 43; starting dose: 2 x 1 tbl. [2 x 200 mg] QD, increasing every 14 days to up to 2 x 2 tbl. [2 x 400 mg] QD according to tolerability) or placebo (n = 40) for up to 24 months. The primary and secondary endpoints of the study were relapse-free survival (RFS) and overall survival, respectively.
- Median follow-up for RFS: 41.8 months (IQR, 24.1–42.5)
- Two-year RFS in patients in the sorafenib and placebo arm, respectively: 85.0% (95% CI, 69.5–93.0) vs 53.3% (95% CI, 36.5–67.5), HR = 0.39 (95% CI, 0.183–0.848), P = 0.013
- Median follow-up for OS: 55.4 months (IQR, 24.1–42.5)
- OS was significantly longer in patients in the sorafenib arm compared to the placebo arm: HR = 0.447 (95% CI, 0.20–0.97), P = 0.03
- The most common grade 3–4 adverse events in the sorafenib and placebo arms were acute GvHD (24% vs 18.2%), gastrointestinal toxicity (14.3% vs 15.4%), and infections (26.3% vs 23.1%)
In an interview with the AML Global Portal (AGP), Andreas Burchert noted that the mature data from the SORMAIN trial demonstrate for the first time, evidence that FLT3 inhibition after allo-SCT is feasible and significantly reduces the risk of relapse and death in patients with FLT3-ITD AML which in turn results in improved survival. He further added that this study has practice-changing implications that will establish a new treatment paradigm for AML.