In a nutshell
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 (abnormal gene). The authors found that this therapy was effective and tolerable after aHSCT in such patients.
Some background
FLT3-ITD (internal tandem duplication in FLT3 gene) mutation is a cancerous genetic abnormality. Patients with AML carrying FLT3-ITD are commonly treated by alloHSCT. This involves transplanting healthy stem cells from a similar donor such a blother or a sister. However, relapse is common in these patients.
Maintenance therapy sustains the benefits of a previous treatment. Sorafenib counteracts various cancerous mutations including FLT3-ITD. Previous studies and small-scale trials suggested that sorafenib maintenance after alloHSCT may reduce relapse in such patients. However, evidence of tolerability and effectiveness is lacking in larger trials.
Methods & findings
The study included 202 adult patients with FLT3-ITD-positive AML who were undergoing alloHSCT. 100 patients received sorafenib maintenance for 30-60 days after alloHSCT. 102 patients from the control group did not receive sorafenib after alloHSCT. 59 patients in the sorafenib group and 57 from the control group were receiving sorafenib before transplantation. Patients were followed up after alloHSCT for 21.3 months on average.
Relapse occurred in 11 patients on sorafenib and 32 in control group after alloHSCT. Average time to relapse was 11.6 months under sorafenib and 5.7 months in the control group. Chances of relapsing during 1-year of alloHSCT were 7% for sorafenib and 24.5% for the control group. The control group had a 75% higher risk of relapse compared to the sorafenib group.
The chances of relapse after 2 years were 11.9% for sorafenib and 31.6% for the control group. The control group had 71% higher risks of relapse after 2 years of alloHSCT, compared to sorafenib.
Overall, 82.1% of patients under sorafenib and 68% in the control group survived for 2 years. Th sorafenib group had a 52% lower risk of death compared to the control group. 78.9% of patients in the sorafenib group and 56.6% in the control group survived without AML for 2 years.
No death occurred due to sorafenib maintenance. Severe medical events happened in both groups within 210 days of alloHSCT. Infections, abnormal blood cell counts and graft vs host disease (GVHD; complication of alloHSCT where the donated cells attack the patients) were common in both groups.
The bottom line
The study concluded that sorafenib maintenance was an effective way to prevent relapse and improve survival in patients with FLT3-ITD-positive AML after alloHSCT.
The fine print
The study was conducted in China only. It also did not include a placebo group. Further studies are needed.
Published By :
The Lancet. Oncology
Date :
Aug 10, 2020
