Sorafenib maintenance therapy significantly reduces the risk of relapse and death after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with FLT3-internal tandem duplication (ITD)–positive acute myeloid leukemia (AML), according to results of a study published in the Journal of Clinical Oncology.

Sorafenib is a multitargeted tyrosine kinase inhibitor. Based on earlier reports, with limited sample sizes, of sorafenib activity in FLT3-ITD-positive AML following allo-HSCT, the SORMAIN trial (German Clinical Trials Register: DRKS00000591), aimed to assess whether sorafenib could prevent recurrence after allo-HSCT in high risk FLT3-ITD–positive AML.

This randomized, placebo-controlled, double-blind phase 2 trial was conducted at 15 centers in Germany and Austria. A total of 83 adult patients (median age, 54 years) with FLT3-ITD–positive AML who were in complete hematologic remission after allo-HSCT were randomly assigned (1:1) to receive either sorafenib (43 patients) or placebo (40 patients) for 24 months. The sorafenib dose was escalated from 400 mg to 800 mg per day over a 6-week period at the start of the trial. The primary endpoint was relapse-free survival (RFS).

Potential prognostic factors were well balanced between the 2 arms of the study. The median duration of therapy was 34.57 weeks (range, 1.29-106.86 weeks) in the sorafenib arm and 54.36 weeks (range, 1.71-128.29 weeks) in the placebo arm.

The median follow-up duration was 41.8 months (interquartile range, 24.1-42.5 months). The median RFS was 30.9 months in the placebo arm and had not yet been reached in the sorafenib arm. The risk of relapse or death was lower in the sorafenib arm compared with the placebo arm (hazard ratio [HR], 0.39; 95% CI, 0.18-0.85; log-rank P =.013). The 24-month RFS probability was significantly higher in the sorafenib arm compared with the placebo arm (85.0% vs 53.3%, respectively; HR, 0.256; 95% CI, 0.10-0.65; log-rank P =.002).

The investigators also conducted an exploratory analysis of minimal residual disease (MRD). None of the 9 patients who were MRD-negative prior to HCT relapsed or died when treated with sorafenib; whereas 5 of 12 (42%) MRD-negative patients in the placebo arm relapsed or died (P =.028).

According to the authors, sorafenib was well tolerated. More patients in the sorafenib arm (9 patients) compared with the placebo arm (2 patients) discontinued treatment due to toxicity. The most common reasons for treatment discontinuation were adverse events among sorafenib-group members (9 patients; 20.93%) and relapse among placebo-group members (17 patients; 42.50%).

The Trial Steering Committee and the independent Data and Safety Monitoring Committee terminated the study prematurely on July 1, 2016, because of slow patient recruitment and inadequate enrollment.

“In conclusion, SORMAIN establishes targeted maintenance therapy as a novel efficacious treatment paradigm with the potential to meaningfully improve outcome after [allo-HSCT],” wrote the authors. “A 2-year sorafenib maintenance therapy should be considered as a new treatment standard for FLT3-ITD–positive AML patients in complete remission after [allo-HSCT].”

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.