Pre-HSCT WT1 Levels Vs ELN 2017 Risk Classification Is a Better Predictor of Outcomes in Intermediate-Risk AML

Although European Leukemia Net 2017 Risk Stratification was ineffective for predicting outcomes following allogeneic hematopoietic stem cell transplantation in intermediate-risk acute myeloid leukemia, pre-transplant Wilms tumor gene 1 expression and FLT3-ITD mutation demonstrated promising predictive ability.

Whereas European Leukemia Net 2017 (ELN 2017) Risk Stratification classification did not appear to accurately predict outcomes post–hematopoietic stem cell transplantation (HSCT) in patients with intermediate-risk acute myeloid leukemia, Wilms tumor gene 1 (WT1) level before transplant and FLT3 ITD mutations showed promising prognostic value.

At a median follow-up of 18 months, the 2-year overall survival (OS) rates in intermediate- and adverse-risk groups were 58.6% and 64.4% (P = .299) following HSCT, respectively. Moreover, the 2-year rates of relapse-free survival (RFS) and cumulative incidence of relapse (CIR) in both respective groups were 50.5% vs 53.7% (P = .533) and 26.9% vs 36.9% (P = .060) following treatment. For the intermediate- and adverse-risk groups, the 2-year nonrelapse mortality (NRM) rates were 29.0% vs 19.6% (P = .015).

WT1 levels prior to HSCT appeared to be more effective in predicting outcomes vs ELN 2017 in the intermediate-risk group vs the adverse-risk group, including 2-year rates of OS (64.2% vs 51.5%; P = .099), RFS (59.4% vs 32.4%; P = .003), and CIR (18.9% vs 60.0%; P <.001). FLT3-ITD appeared to have the most significant impact on outcomes across all ELN 2017 components vs pre-HSCT WT1 level in the intermediate- and adverse-risk groups, with the FLT3 ITD–mutated subgroup experiencing the worse outcomes regardless of allelic ratios or NPM1 mutation status.

The population included a total of 174 patients with intermediate- and adverse-risk disease who received allogeneic HSCT between November 2017 to November 2020. Treatment for the population consisted of anthracycline and cytarabine intensive chemotherapy followed by consolidation allogeneic HSCT once a complete response (CR) or CR with incomplete peripheral recovery was achieved.

Of those who were included in the study, 62% had intermediate risk and 38% had adverse risk disease. Median age at transplant was 54 years and 37.9% had hematopoietic stem cell transplant–specific comorbidity index of 3 or more at transplant. A total of 79.3% of patients underwent myeloablative conditioning transplants. Moreover, patients most commonly received haploidentical donor transplants (43.7%), matched unrelated donor transplants (26.4%), matched sibling donors (25.9%), and mismatched unrelated donors or umbilical cord blood (4%).

The probability of OS and RFS at 2 years following transplant was 60.7% (95% CI, 53.6%-68.9%) and 51.8% (95% CI, 44.6%-60.1%), respectively. Moreover, the 2-year CIR rate for the overall cohort was 31.2% (95% CI, 23.9%-38.8%) and the NRM rate was 22.3% (95% CI, 16.0%-29.3%).

Additional findings from the study indicated that being 55 years or older (HR, 3.90; 95% CI, 1.66-9.15; P = .002) and having ELN 2017 advanced-risk disease (HR, 0.39; 95% CI, 0.17-0.86; P = .02) were associated with a higher and lower risk of NRM. In the intermediate-risk group, WT1-low patients had a 2-year OS rate of 66.9% vs 58.7% (P = .162) in the WT1-high group. Moreover, the 2-year RFS, CIR, and NRM rates in the WT1-low and -high groups were 59.5% vs 21.6% (P = .009), 12.0% vs 67.3% (P <.001), and 32.1% vs 18.4% (P = .084%), respectively.

In the adverse-risk group, the 2-year OS rate was 66.9% in WT1-low patients and 58.7% in WT1-high patients (P = .325). Moreover, the RFS, CIR, and NRM rates in each respective group were 58.9% vs 43.4% (P = .189), 19.2% vs 51.9% (P = .031), and 13.4% vs 5.6% (P = .295). Two-year OS and RFS rates for the FLT3 ITD–high/NPM1-mutant group (46.2% and 30.0%), FLT3 ITD–low/NPM1 wild-type (44.4% and 33.3%) group, and FLT3 ITD–high/NPM1 wild-type (50.0% and 36.4%) group did not differ significantly. Investigators reported that the aforementioned subgroups had worse OS and RFS outcomes vs the FLT3 ITD–negative group who were with intermediate or adverse risk.

Reference

Kim TY, Park S, Kwag D, et al. Depth of response to intensive chemotherapy has significant prognostic value among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic stem-cell transplantation with intermediate or adverse risk at diagnosis compared to at-risk group according to European Leukemia Net 2017 Risk Stratification. Cancers (Basel). 2022;14(13):3199. doi:10.3390/cancers14133199