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. 2023 Feb 14;7(3):436-444.
doi: 10.1182/bloodadvances.2021005789.

Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation

Marius Bill  1   2   3 , Madlen Jentzsch  1 , Lara Bischof  1 , Jessica Kohlschmidt  4 , Juliane Grimm  1 , Laura Katharina Schmalbrock  1 , Donata Backhaus  1 , Dominic Brauer  1 , Karoline Goldmann  1 , Georg-Nikolaus Franke  1 , Vladan Vucinic  1 , Dietger Niederwieser  1 , Alice S Mims  4 , Uwe Platzbecker  1 , Ann-Kathrin Eisfeld  4 , Sebastian Schwind  1
Affiliations

Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation

Marius Bill et al. Blood Adv. .

Abstract

Somatic mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML). The prognostic impact of the presence of IDH mutations may be influenced by the comutational status, the specific location of the mutation (ie, IDH1 R132, IDH2 R140, and IDH2 R172) at diagnosis, and the dynamics of the mutation burden during disease course. Even though many patients with IDH-mutated AML are consolidated by hematopoietic stem cell transplantation (HSCT), the underlying biology and prognostic consequences remain largely unknown. Here, we present a large analysis of 292 patients with AML who received HSCT in complete remission (CR) or CR with incomplete peripheral recovery (CRi), in which we assessed the IDH mutation status at diagnosis and HSCT as a potential marker for measurable residual disease (MRD). About a quarter of all patients were IDH-mutated at diagnosis. The diagnostic presence of IDH mutations in AML did not have a significant prognostic impact when consolidated with HSCT. However, IDH1 R132 and IDH2 R172 MRD positivity in remission at HSCT associated with an increased risk of relapse, while IDH2 R140 mutations did not. The IDH2 R140 variant allele frequency (VAF) at diagnosis was higher, clustering around 50%, and the mutation clearance at HSCT in morphologic remission was much lower compared with IDH1 R132 and IDH2 R172. In our cohort, IDH2 R140 mutations behaved more like a clonal hematopoiesis-related aberration, while IDH1 R132 and IDH2 R172 harbored AML disease-specific features.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Characteristics and outcomes according to IDH mutation status at diagnosis. (A) Comutations in patients with IDH mutation (ie, IDH1 R132, IDH2 R140, IDH2 R172) and wild-type at diagnosis (n = 125) consolidated by HSCT. (B) BM VAF at diagnosis according to IDH mutation status. (C) CIR, (D) EFS, and (E) OS of HSCT-consolidated patients with AML according to IDH mutation status.
Figure 2.
Figure 2.
IDH mutation (ie, IDH1 R132, IDH2 R140, IDH2 R172) frequency, CIR, EFS, and OS of HSCT-consolidated patients with AML according to the ELN2017 risk groups. (A) ELN2017 favorable, (B) ELN2017 intermediate, and (C) ELN2017 adverse.
Figure 3.
Figure 3.
Characteristics and outcomes according to IDH mutation status at HSCT. (A) ddPCR-based MRD at HSCT in patients with IDH-mutated (ie, IDH1 R132, IDH2 R140, IDH2 R172) AML. (B) Pre-HSCT MRD VAF according to IDH mutation status. (C) CIR, (D) EFS, and (E) OS of HSCT-consolidated patients with AML according to optimized IDH MRD status (IDH1 R132 or IDH2 R172 MRD-positive n = 5; IDH2 R140 MRD-positive n = 11; IDH MRD-negative n = 28).
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References

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