Sorafenib Maintenance After Allogeneic HCT in Patients With FLT3-ITD–Positive AML

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In the German-Austrian phase II SORMAIN trial reported in the Journal of Clinical Oncology, Burchert et al found that maintenance treatment with sorafenib vs placebo was associated with significantly prolonged relapse-free survival after allogeneic hematopoietic stem cell transplantation (HCT) in patients with acute myeloid leukemia (AML) with a FLT3–internal tandem duplication (ITD) mutation.

As stated by the investigators, “Despite undergoing allogeneic HCT, patients with AML with FLT3-ITD have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT.”

Study Details

In the multicenter double-blind trial, with screening between October 2010 and May 2016, 83 adult patients in complete hematologic remission after HCT were randomly assigned to receive sorafenib (n = 43) or placebo (n = 40) daily for 24 months or until relapse or unacceptable toxicity. The dose of sorafenib was increased from 200 mg twice daily for 2 weeks to 300 mg twice daily for 4 weeks and to 400 mg twice daily thereafter. The primary endpoint was relapse-free survival.

Relapse-Free Survival


  • Sorafenib significantly prolonged relapse-free survival vs placebo.
  • Median relapse-free survival was not reached vs 30.9 months, with 24-month rates of 90.5% vs 66.2%.

At the time of relapse-free survival data lock, median follow-up for relapse-free survival was 41.8 months. Median relapse-free survival was not reached in the sorafenib group vs 30.9 months in the placebo group (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.18–0.85, P = .013). The estimated probability of relapse-free survival at 24 months was 85.0% (95% CI = 0.70%–0.93%) vs 53.3% (95% CI = 0.36%–0.68%; HR = 0.256, 95% CI = 0.10–0.65, P = .002). In exploratory analysis, the relapse-free survival benefit of sorafenib was enhanced among patients with undetectable minimal residual disease (MRD) before HCT (P = .028 vs placebo) and in those with detectable MRD after HCT (P = .015 vs placebo).

After median follow-up of 55.1 months for overall survival, median overall survival was not reached in either group (HR = 0.52, 95% CI = 0.24–1.11, P = .086). The estimated probability of overall survival at 24 months was 90.5% vs 66.2% (HR = 0.241, 95% CI = 0.08–0.74, P = .007).

Adverse Events

The most common grade ≥ 3 adverse events in both the sorafenib and placebo groups were acute or chronic graft-vs-host disease (76.8% vs 59.8%). Other common grade ≥ 3 adverse events were infections (26.2%), gastrointestinal toxicity (14.3%), electrolyte alterations (14.3%), and skin toxicity (11.9%) in the sorafenib group and infections (23.1%) and gastrointestinal toxicity (15.4%) in the placebo group. Adverse events led to study treatment discontinuation in 22.0% vs 5.0% of patients. Two of 16 deaths during the study period were unrelated to AML, with both occurring in the placebo group.

The investigators concluded, “Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for [patients with] FLT3-ITD–positive AML.”

Andreas Burchert, MD, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Deutsche Forschungsgemeinschaft, German Carreras Leukemia Foundation, and Bayer HealthCare. For full disclosures of the study authors, visit

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