The prognosis of AML with other gene mutations in different IDH mutation subgroups is different

The incidence of IDH1 and IDH2 mutations in adult acute myeloid leukemia (AML) patients is 7%-14% and 8%-19%, respectively
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Although there are common carcinogenic mechanisms, different IDH mutation subtypes (IDH1, IDH2R140 and IDH2R172) may have different patterns of genetic changes
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In AML patients treated with intensive chemotherapy (IC), the risk stratification within each IDH mutation subtype has not yet been elucidated
.

Based on this, some researchers retrospectively analyzed the prognosis of newly diagnosed AML patients with IDH mutation who received IC treatment based on data from three prospective clinical trials of the French Acute Leukemia Association (ALFA)
.

The editor organizes its main content as follows for the reference of readers
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Research methods All patients received induction therapy (including anthracyclines and cytarabine)
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Patients with adverse risks who have sibling-matched donors or HLA10/10 HLA-matched irrelevant donors should undergo hematopoietic stem cell transplantation (HSCT) consolidation therapy
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Study Results 1 Patient characteristics The study analyzed a total of 319 IDH1/2 mutations from prospective clinical trials of ALFA-0701 (n=58), ALFA-0702 (n=132) and ALFA-1200 (n=129).
AML patients, including 127 (40%) IDH1 mutation AML patients, 135 (42%) IDH2R140 mutation and 57 (18%) IDH2R172 mutation AML patients
.

The median age of the overall patient is 61 years (range: 52-67 years), and male patients account for 52%; most patients have a normal karyotype (67%); according to the European Leukemia Network (ELN) 2010 standard, low-risk and intermediate-risk -1, Intermediate-risk-2 and high-risk patients accounted for 29%, 38%, 25%, and 8%, respectively
.

In the IDH1 mutation subgroup of patients, 60 cases (47%) had p.
R132C mutation, 44 cases (35%) had p.
R132H mutation, 11 cases (9%) had p.
R132G mutation, and 10 cases (8%) There was a p.
R132S mutation, and 2 cases (1%) had a p.
R132L mutation
.

In the IDH2R140 mutation subgroup, 127 cases (94%) had p.
R140Q mutation, 7 cases (5%) had p.
R140W mutation, and 1 case (1%) had p.
R140L mutation
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In the IDH2R172 mutation subgroup of patients, 56 cases (98%) had p.
R172K mutation, and 1 case (2%) had p.
R172S mutation
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2 The prognostic factors of IDH1R132 mutation cohort patients.
NPM1 mutation status is the only variable that affects the overall survival (OS) of patients in this cohort.
The 3-year OS rate of NPM1 mutation patients is 65% and the 3-year OS rate of NPM1 wild-type patients is 28% (HR: 0.
29, 95% CI: 0.
16-0.
54; P=0.
0001)
.

Whether the prognostic factors related to the 3IDH2R140 mutation cohort are normal karyotypes (3-year OS rate 67% vs 28% [HR: 0.
38; 95% CI: 0.
19-0.
78; P=0.
008]) and whether there is NPM1 mutation (3-year OS The rate of 77% vs 40% [HR: 0.
41; 95% CI: 0.
21-0.
81; P=0.
01]) is a related factor affecting OS in this cohort
.

4 IDH2R172 mutation cohort patients with prognosis-related factors platelet count is the only factor that affects the patient’s OS.
Using 100×109/L as the platelet cut-off value, the 3-year OS rate of patients with thrombocytopenia is 17%, while that of patients without thrombocytopenia is 3 The annual OS rate was 52% (HR: 0.
19; 95% CI: 0.
07-0.
53; P=0.
002)
.

The effect of 5HSCT on patients with IDH mutations In this study, 197 patients were eligible for HSCT after the first complete remission (CR1)
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Overall, 71 patients (36%) finally received HSCT, and the median time for HSCT was 5.
3 months after diagnosis
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In the IDH1R132 mutation, IDH2R140 mutation, and IDH2R172 mutation cohort, 23 (33%), 28 (36%), and 20 (39%) patients received HSCT, respectively
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Further analysis showed that this part of patients undergoing HSCT at CR1 was associated with prolonged OS (HR: 0.
60; 95% CI: 0.
37-0.
96; P=0.
03) and prolonged disease-free survival (DFS) (HR: 0.
55; 95% CI) : 0.
34-0.
89; P=0.
02) correlation
.

6 The impact of IDH subtypes on the prognosis of patients The results of the correlation analysis between IDH subtypes and prognosis showed that only IDH1R132 mutations are beneficial to OS (HR: 0.
48; 95% CI: 0.
23-0.
99; P=0.
048), and patients with IDH2R172 mutation subtypes have DFS Improvement trend (HR: 0.
41; 95% CI: 0.
14-1.
20; P=0.
10)
.

The study concluded that NPM1 mutation is the main factor affecting OS in newly diagnosed AML patients who receive IC therapy and have IDH1 or IDH2R140 mutations
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According to the 2010 ELN standard, high-risk, newly diagnosed AML patients with IDH mutations who undergo HSCT at CR1 have longer OS and DFS
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References: Matthieu Duchmann, Jean-Baptiste Micol, Nicolas Duployez, et al.
Prognostic significance of concurrent gene mutations in intensively treated patients with IDH-mutated AML:an ALFA study.
Blood.
2021 May 20;137(20):2827- 2837.
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