Photo Credit: Nemes Laszlo

The following is a summary of “Benefit of Allogeneic Transplant in 1st Complete Remission in NPM1 Mutated AML with or without FLT3 ITD Is Restricted to Those Testing MRD Positive after Induction – an Analysis of the UK NCRI AML17 and AML19 Studies,” published in the December 2023 issue of Hematologyby Othman et al.

The role of allogeneic transplantation (allo-HCT) in first complete remission (CR1) for patients with intermediate-risk AML remains controversial, especially in the context of FLT3-Internal Tandem Duplication (ITD) mutations.

Researchers analyzed data from the UK NCRI AML17 and AML19 trials to assess the impact of allo-SCT on NPM1 mutated AML (NPM1 ^mut) AML patients in CR1, considering MRD status.

They conducted 2 trials, NCRI AML17 (April 2009 – December 2014) and AML19 (November 2015 – November 2020), for younger adults with newly diagnosed AML. AML17 based CR1-allo decisions on a validated risk score, while AML19 recommended CR1-allo for NPM1 ^mut patients testing MRD positive post cycle 2. This evaluates NPM1 ^mut patient outcomes, assessing CR1-allo benefits based on FLT3 ITD and molecular MRD status using Kaplan-Meier analysis and time-dependent Cox regression with Simon-Makuch plots. Molecular relapses were considered relapse events, excluding alloSCT after molecular relapse from CR1.

The results showed 737 NPM1 ^mut AML patients achieving CR/CRi with a valid PC2 PB MRD result. PB PC2 MRD positivity was 17% in AML17 and 21% in AML19. CR1-allo rates were 20% (AML17) and 25% (AML19) overall. For MRD+ patients, CR1-allo rates were 27% (AML17) and 60% (AML19). MRD- patients had CR1-allo rates of 18% (AML17) and 16% (AML19). In AML17, MRD+ patients had poor outcomes (3y CIR 84%, OS 25%) and improved in AML19 (3y CIR 50%, OS 51%). CR1-allo significantly benefited MRD+ patients in both trials (3y OS 61% vs. 24%, HR 0.42, P<0.001). MRD- patients had excellent outcomes (3y CIR 33% and 24%, 3y OS 75% and 83% for AML17 and AML19). AlloSCT in CR1 did not provide a survival advantage for MRD- patients (HR 0.83, P=0.4).

For 286 NPM1 ^mut FLT3 ITD ^mutAML patients with a PC2 PB MRD result, 28% were PB PC2 MRD+. CR1-allo was performed in 40% of MRD+ patients (28% in AML17 and 49% in AML19). AML19 exhibited improved outcomes in these high-risk patients (3y CIR 91% vs 68%, 3y OS 22% vs 31%). CR1-allo correlated with improved outcomes (3y OS 45% vs 18%, HR 0.52, 95% CI 0.29-0.93, P=0.03). In 70% of NPM1 ^mut FLT3 ITD ^mut AML patients achieving PB PC2 MRD-, AML17 (3y CIR 37%, 3y OS 75%) and AML19 (3y CIR 27%, 3y OS 80%) showed positive outcomes. CR1-allo was done in 20% (19% AML17, 21% AML19) with no survival benefit (HR 0.80, 95% CI 0.37-1.72, P=0.6), even for those with high FLT3 ITD allelic ratio (HR 0.63, 95% CI 0.2 – 2.23, P=0.50), and no interaction was observed for MRD-negative patients (P=0.86).

They concluded that molecular MRD effectively guided the selection of patients with NPM1 ^mut AML for allogeneic transplantation in first complete remission, demonstrating its utility in tailoring post-remission therapy.

Source: ash.confex.com/ash/2023/webprogram/Paper179033.html