In a Chinese phase III trial reported in The Lancet Oncology, Xuan et al found that sorafenib maintenance after allogeneic hematopoietic stem cell transplantation significantly reduced the risk of relapse vs no maintenance therapy in patients with FLT3–internal tandem duplication (ITD)–positive acute myeloid leukemia.

Study Details

In the multicenter open-label trial, 202 patients were randomly assigned between June 2015 and July 2018 to receive sorafenib maintenance at 400 mg twice daily (n = 100) or no maintenance (control, n = 102) at 30 to 60 days posttransplantation. Sorafenib treatment was continued until day 180.

Patients had to have composite complete remission before and after transplantation and hematopoietic recovery within 60 days after transplantation. The primary endpoint was 1-year cumulative incidence of relapse in the intention-to-treat population.

Incidence of Relapse

Median follow-up posttransplantation was 21.3 months. The 1-year cumulative incidence of relapse was 7.0% in the sorafenib group vs 24.5% in the control group (hazard ratio [HR] = 0.25, P = .0010). Median time to relapse was 11.6 months vs 5.7 months (P = .16). At 2 years, the cumulative incidence of relapse was 11.9% vs 31.6% (HR = 0.29, P < .0001).

Nonrelapse mortality at 2 years was 9.2% vs 11.8% (HR = 0.69, P = .49). Overall survival at 2 years was 82.1% vs 68.0% (HR = 0.48, P = .012). Leukemia-free survival at 2 years was 78.9% vs 56.6% (HR = 0.37, P < .0001).

Toxicity

Within 210 days after transplant, grade 3 or 4 adverse events occurred in 50% of the sorafenib group vs 46% of the control group, with the most common being infections (25% vs 24%), acute graft-vs-host-disease (23% vs 21%), chronic graft-vs-host-disease (18% vs 17%), and hematologic toxicity (15% vs 7%). Secondary malignant disease occurred in two patients (2%) in each group. The most common serious adverse events in both groups were acute graft-vs-host-disease (22% vs 19%) and infections (15% vs 16%).

Adverse events led to death in four patients in the sorafenib group (due to infection in 2, acute graft-vs-host-disease in 1, and cardiotoxicity in 1) and five patients in the control group (due to infection in 3, acute graft-vs-host-disease in 1, and thrombotic microangiopathy in 1). None of the deaths was considered related to treatment.

The investigators concluded: “Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukemia.”

Qifa Liu, MD, of the Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, is the corresponding author for The Lancet Oncology article.

Disclosure: For full disclosures of the study authors, visit thelancet.com.