Treating acute myeloid leukemia with FLT3-ITD mutation by sorafenib maintenance after HSCT

The study evaluated outcomes of sorafenib (Nexavar) maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutation. The authors found that sorafenib maintenance therapy decreased the risks of relapse and mortality after HSCT in such patients.

FLT3-ITD (internal tandem duplication in the FLT3 gene) mutation is a cancerous genetic abnormality. Patients with AML carrying FLT3-ITD are traditionally treated by an alloHSCT. However, they often relapse or die after alloHSCT.

Maintenance therapy sustains the benefits of a previous treatment. Sorafenib is a targeted therapy that counteracts various cancerous mutations including FLT3-ITD. The effects of sorafenib maintenance therapy after an alloHSCT in patients with AML and FLT3-ITD mutations are unclear.

The study included 83 adult patients with FLT3-ITD–positive AML. They were in complete hematologic remission (CHR) after an alloHSCT. CHR is achieved when less than 5% leukemic cells are left in the bone marrow. 43 patients received sorafenib maintenance for 24 months and 40 received a placebo. The average follow-up time was 41.8 months.

Patients on placebo survived for 30.9 months without relapse on average. Patients on sorafenib still experienced no relapse during analysis, at the end of follow-up. The placebo group had a 61% higher risk of relapse compared to sorafenib. The chances of surviving 24-months without relapse were 85% for sorafenib and 53.3% for placebo.

The placebo group had 48% higher risks of mortality compared to sorafenib. Overall, the chances of surviving 24-months were 90.5% for sorafenib and 66.2% for placebo.

Minimal residual disease (MRD) refers to the small leukemic cell number left in patients’ bodies after treatment. 5 of 12 patients without MRD before alloHSCT relapsed under placebo. No MRD-negative patient relapsed or died on sorafenib.

Sorafenib was generally well tolerated. 48.8% of patients in the sorafenib group needed to lower the doses. This was compared to 40% of the placebo group. The most common severe side effects in both groups was graft-vs-host disease (GvHD). GvHD occurs when donor stem cells attack the patient's healthy cells. This happed in 76.8% of the sorafenib group and 59.8% of the placebo group.

The study concluded that maintenance therapy with sorafenib reduced risks of relapse and death compared to placebo, in patients with FLT3-ITD-positive AML after alloHSCT.

The average treatment duration was different for each group in this study. It was 54.36 weeks for placebo and 34.57 weeks for sorafenib. Also, the number of patients was low. Further studies are needed.