Sorafenib Maintenance Post-Transplantation Among Patients With FLT3-ITD Mutated AML

Results from a Randomized Phase 3 Clinical Trial

According to findings from a randomized phase 3 clinical trial recently published in BMC Medicine, the use of sorafenib maintenance post-transplantation yielded safe results among patients with FLT3-internal tandem duplication (FLT3-ITD) mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT).

Xin Xu, MD, Southern Medical University, Guangzhou, China, and coauthors stated that although there has been an increase in research surrounding multi-kinase inhibitors and their correlation with opportunistic infections, “the effect of sorafenib on [Epstein-Barr virus] and [cytomegalovirus] infections in sorafenib-treated patients remains unclear.” 

To expand on this gap in research, Xu et al aimed to assess a primary endpoint of risk of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections within 3 years post-transplantation. Secondary endpoints included cumulative incidences of relapse, non-relapse mortality, overall survival, leukemia-free survival, and GVHD-free/relapse-free survival at 3 years. 

202 patients with FLT3-ITD mutated AML undergoing alloHSCT at the time (median age: 35 years) were enrolled in this study. Patients were assigned to either the sorafenib cohort (n=100) or the control cohort (n=102). Patients in the sorafenib cohort received sorafenib 30 to 60 days post-transplantation and continued until day 180, while patients in the control group did not receive sorafenib or any other kinase inhibitor unless the patient experienced a relapse. All patients received a modified busulfan-cyclophosphamide regimen. 
Results indicated that 22% of the sorafenib cohort (n=22) experienced EBV-DNAemia, which was comparable to 22.5% (n=23) of the control cohort. At 3 years, the cumulative incidence of EBV-associated diseases, including but not limited to EBV-PTLD, EBV-enteritis, and EBV-encephalitis, was 5.0% in the sorafenib arm and 5.9% in the control arm, respectively. The 3-year mortality rate of EBV-associated diseases was 0% in the sorafenib arm and 1% in the control arm, respectively. 

54% of the sorafenib arm (n=4) experienced CMV-DNAemia, which was also comparable to   52% of the control arm (n=53). The 3-year cumulative incidence of CMV-DNAemia was 56% in the sorafenib arm and 52.9% in the control arm, respectively. At 3 years, the cumulative incidence of CMV-associated diseases was 8.0% in the sorafenib arm and 8.8% in the control arm, respectively.

The overall survival rate was 79% in the sorafenib arm (n=79) versus 61.4% in the control arm (n=63), respectively, with causes of death including leukemia relapse, infections, graft-versus-host disease (GVHD), EBV-PTLD, thrombotic microangiopathy, and acute left heart failure. At 3 years, the leukemia-free survival rate was 75.9% in the sorafenib arm and 52.5% in the control arms and the GVHD-free/relapse-free survival was 65.8% and 46.6%.

As all endpoints were reached, “Sorafenib maintenance post-transplantation does not increase the incidence and mortality of EBV and CMV infections, demonstrating a favorable safety profile,” Xu and colleagues concluded.

Source: 

Xu X, Fan Z, Wang Y, et al. Effect of sorafenib maintenance on Epstein-Barr virus and cytomegalovirus infections in patients with FLT3-ITD AML undergoing allogeneic hematopoietic stem cell transplantation: a secondary analysis of a randomized clinical trial. BMC Medicine. Published online September 2, 2022. doi:https://doi.org/10.1186/s12916-022-02479-x