For patients with FLT3-internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML) who receive allogeneic hematopoietic stem cell transplantation (allo-HSCT), sorafenib maintenance after transplantation may reduce relapse and could be a therapeutic option, according to results from an open-label, randomized trial published in The Lancet Oncology.

Previous retrospective studies have provided evidence suggesting the administration of sorafenib pretransplantation or posttransplantation may reduce relapse or improve survival in this patient population. Currently, data from randomized trials are not available, and sorafenib maintenance posttransplantation is recommended as B-II evidence level.

A team of investigators conducted a phase 3 trial ( Identifier, NCT02474290) at 7 hospitals in China to determine the efficacy and tolerability of sorafenib maintenance posttransplantation in this patient population for the prevention of relapse.

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Patients who were aged 18 to 60 years, had FLT3-ITD AML, were undergoing allo-HSCT, had an Eastern Cooperative Oncology Group performance status of 0 to 2, had composite complete remission before and after transplantation, and had hematopoietic recovery within 60 days following transplantation were eligible to participate in the analysis.

A total of 202 participants were randomly assigned to receive either sorafenib maintenance (100 patients) or nonmaintenance control (102 patients) at 30 to 60 days after transplantation. Patients in the sorafenib arm were administered an oral dose of 400 mg twice a day. The primary outcome was the 1-year cumulative relapse incidence among patients treated with sorafenib.

The median follow-up was 21.3 months posttransplantation. Among patients treated with sorafenib, the median treatment use pretransplantation was 119 days. Relapse was reported in 11 patients in the sorafenib cohort and 35 patients in the control cohort; 7.0% of the sorafenib arm and 24.5% of the control arm has a 1-year cumulative incidence of relapse (hazard ratio [HR], 0.25; 95% CI, 0.11-0.57; P =.0010). The 2-year cumulative incidence of relapse for sorafenib and control arms were 11.9% and 31.6%, respectively (HR, 0.29; 95% CI, 0.15-0.58; P <.0001).

Among participants in the sorafenib and control groups, the most common grade 3 and 4 adverse events were infections (25% vs 24%, respectively), acute graft-vs-host-disease (23% vs 21%, respectively), chronic graft-vs-host disease (18% vs 17%, respectively), and hematological toxicity (15% vs 7%, respectively). The authors noted that there were no treatment-related mortalities.

One limitation to the investigation was the non-blinded and non-placebo-controlled nature of the trials. The authors noted that this “might carry a higher risk of bias on the part of both the treatment doctor and the patient, usually in favour of the investigational arm.”

“Sorafenib maintenance post-transplantation could be a therapeutic option for FLT3-ITD acute myeloid leukaemia,” the investigators wrote. “Whether prolonging sorafenib maintenance post-transplantation is more beneficial than the duration of maintenance we studied here needs further investigation.”

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


Xuan L, Wang Y, Huang F, et al. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol. Published online August 10, 2020. doi:10.1016/s1470-2045(20)30455-1