Allo-SCT, MRD Negativity Associated With Better Outcomes in AML With Certain Mutations

Hoping to offer a better understanding of appropriate postremission therapy (PRT) for patients with intermediate-risk acute myeloid leukemia (IR-AML), researchers are detailing their findings on clinical and molecular factors that impact prognosis in certain patients with AML.

Their retrospective findings, recently published in Hematology, shed light on the role of minimal residual disease (MRD) status and type of PRT in the prognosis of patients with IR-AML who do not have FLT3-ITD, NPM1, and biallelic CEBPA mutations.

According to the researchers, these findings have relevant implications because the role of molecular genetics is increasingly being utilized in prognostic assessment of patients, particularly in IR-AML.

“In general, NPM1^mut/FLT3-ITD^mut-neg or CEBPA^dm provides a good prognosis for IR-AML, whereas IR- AML with FLT3-ITD^mut has a poor prognosis,” explained the researchers. “For the subgroup of patients with IR-AML negative for NPM1^mut, CEBPA^dm, and FLT3-ITD^mut (here referred to as NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML), the risk–benefit ratio of [allogeneic hematopoietic stem cell transplantation] is poorly defined.”

The study included 64 patients with intermediate-risk disease, of which 28 had NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML that had achieved a complete response.

Altough 17 of the patients analyzed in the study received postremission chemotherapy (PR-CT), 11 received allogeneic hematopoietic stem cell transplantation (allo-HSCT), which was associated with improved overall survival (OS) and relapse-free survival (RFS), as well as reduced cumulative incidence of relapse (CIR). Independently, allo-HSCT was also associated with favorable OS.

According to the researchers, the increased survival benefit seen with allo-HSCT over PR-CT may be explained by the lower risk of relapse—an independent adverse factor for prognosis—associated with allo-HSCT, as well as its better CIR.

Unsurprisingly, MRD negativity prior to PRT was independently associated with favorable OS.

“Thus, we further performed a subgroup analysis. For patients with NPM1^mut-negCEBPA^dm-negFLT3-ITD^neg AML, allo-HSCT also improved the OS and RFS of patients who obtained MRD^pos or MRD^neg compared with PR-CT (OS, P = .012 and P = .036, respectively; RFS, P = .030 and P = .047, respectively),” wrote the researchers.

The lack of molecular profiling data for some of the participants and the small sample size were noted as study limitations for generalizing interpretation of these findings.

Reference

Zheng W-S, Hu Y-L, Guan L-X, Peng B, Wang S-Y. The effect of the detection of minimal residual disease for the prognosis and the choice of post-remission therapy of intermediate-risk acute myeloid leukemia without FLT3-ITD, NPM1 and biallelic CEBPA mutations. Hematology. 2021;26(1):179-185. doi:10.1080/16078454.2021.1880753