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The European LeukemiaNet (ELN) released an update to their 2022 recommendations in 2022 following changes in the classification of acute myeloid leukemia (AML), genomic diagnostics, and molecular markers. The AML Hub has previously covered the ELN recommendations, including the updated 2022 ELN classification.
During the European Hematology Association (EHA) 2023 Congress, Bill.1 presented validation of the updated 2022 ELN risk stratification in adult patients with AML. In addition, Rausch et al.2 recently published a study on the validation and refinement of the 2022 ELN genetic risk stratification of AML. As part of our editorial theme on navigating the recent updates to the classification of AML, we are pleased to summarize their key findings.
A large cohort study in adult patients with newly diagnosed AML treated within the German Study Alliance Leukemia trials. The median age of included patients was 54 years (range, 18–89 years).
At a median follow-up of 6.9 years, 1,570 patients were classified according to the 2022 ELN classification. Comparison of pretreatment parameters based on the ELN groups revealed significant differences (Table 1).
Table 1. Pretreatment parameters based on 2022 ELN groups*
Pretreatment parameters, % (unless stated otherwise) |
Favorable-risk |
Intermediate-risk |
Adverse-risk |
p value |
---|---|---|---|---|
Median age (range), years |
51 (18–85) |
55 (18–85) |
56 (18–89) |
<0.001 |
Diagnosis |
|
|
|
<0.001 |
de novo AML |
94.2 |
86.5 |
72.3 |
|
sAML |
3.8 |
10.6 |
22.3 |
|
tAML |
1.9 |
3.0 |
5.4 |
|
Median WBC count (range), 109/L |
27.5 (0.3–453) |
23.4 (0.6–466) |
9.2 (0.4–450) |
<0.001 |
Median blood blasts (range) |
45 (0–98) |
45 (0–100) |
28 (0–99) |
<0.001 |
Median bone marrow blasts (range) |
64 (7–96) |
68 (20–100) |
56 (20–100) |
<0.001 |
ELN, European LeukemiaNet; sAML, secondary acute myeloid leukemia; tAML, therapy-related acute myeloid leukemia; WBC, white blood cell. |
Differences between the 2022 ELN groups in complete remission (CR), disease-free survival, and overall survival (OS) are shown in Table 2. Although 21% (n = 340) of patients were reclassified using 2022 ELN recommendations compared with 2017 ELN recommendations, the net effect on the percentage of patients reclassified was minimal (favorable-risk group, −0.7%; intermediate-risk group, −3.4%; adverse-risk group, +4.1%). The movement to each reclassified risk group was due to:
Patients reclassified according to the 2022 vs 2017 ELN recommendations showed an improved 3-year OS (p = 0.001) and allowed better separation of the risk groups.
Table 2. Survival outcomes based on 2022 ELN groups*
Survival outcomes, % (unless stated otherwise) |
Favorable-risk |
Intermediate-risk |
Adverse-risk |
p value |
---|---|---|---|---|
CR |
87.3 |
76.6 |
49.2 |
<0.001 |
5-year OS |
53 |
32 |
13 |
<0.001 |
5-year DFS |
49† |
32‡ |
23§ |
<0.001 |
CR, complete remission; DFS, disease-free survival; ELN, European LeukemiaNet; OS, overall survival. |
In a cohort study of patients with newly diagnosed AML treated with cytarabine-based induction chemotherapy in two German AML Cooperative Group trials, the median age was 58 years (range, 18–86 years). The validation cohort included 1,160 patients with AML, of which 83% were aged <60 years and received intensive induction chemotherapy.
A total of 1,118 patients were classed according to the 2022 ELN classification (Figure 1).
Figure 1. 2022 ELN categories stratified by age and sex*
ELN, European LeukemiaNet.
*Adapted from Rausch, et al.2
Figure 2 shows response and survival rates for patients classified by 2022 ELN risk groups.
Figure 2. CR, RFS, and OS rates for 2022 ELN risk groups*
CR, complete remission; ELN, European LeukemiaNet; OS, overall survival; RFS, relapse-free survival.
*Adapted from Rausch, et al.2
Patients reclassified from the 2017 ELN intermediate- to 2022 ELN adverse-risk group demonstrated improved 5-year OS (Figure 3). Patients reclassified from the 2017 ELN adverse- to the 2022 ELN intermediate-risk group had numerically worse 5-year OS. The OS was also significantly worse compared with those reclassified from the favorable- to intermediate-risk group (p = 0.016).
Figure 3. OS in patients reclassified from ELN 2017 to ELN 2022*
ELN, European LeukemiaNet; OS, overall survival.
*Adapted from Rausch, et al.2
†Statistically significant.
Allogeneic hematopoietic stem cell transplantation in the first CR was associated with 2022 ELN risk groups (18% of favorable-, 30% of intermediate-, and 34% of adverse-risk patients; p < 0.0001). Patients in the adverse-risk group receiving allogeneic hematopoietic stem cell transplantation in the CR had improved OS (p = 0.032). In addition, OS was superior in patients in intermediate- and adverse-risk groups with low FLT3- internal tandem duplication (ITD) compared with high FLT3-ITD (45% vs 27%; p = 0.097 and 25% vs 10%; p = 0.027, respectively).
Based on the presence of myelodysplasia-related (MR) mutations, 45% of reclassified patients moved from the 2017 ELN favorable- and intermediate-risk groups to the 2022 ELN adverse-risk group. 5-year RFS (p = 0.0035) and OS (p = 0.0004) were improved in patients with MR mutations vs other adverse-risk mutations. The validation cohort confirmed improved 5-year OS for patients reclassified to the adverse-risk group with MR mutations compared with other adverse-risk patients (30% vs 18%, p = 0.0052). However, OS was significantly worse in reclassified patients with MR mutations than the remaining intermediate-risk group (p = 0.02).
The authors proposed refinement of the 2022 ELN risk classification system to include very favorable- and very adverse-risk groups, without any additional genetic markers.
Figure 4. Validation of proposed refinement of 2022 ELN classification for CR and OS rates *
CR, complete remission; ELN, European LeukemiaNet; OS, overall survival.
*Adapted from Rausch, et al.2
The study found the 2022 ELN risk stratification more predictive than the ELN 2017 risk stratification, with minimal impact despite a 21% reclassification rate. Additional analysis on secondary mutations in the adverse-risk group is needed.
The study by Rauch et al.2 showed the 2022 ELN classification assigned more patients to an adverse-risk group, yielding better outcomes than the 2017 ELN adverse-risk group. The inclusion of MR mutations outlines the need to consider them in the intermediate-risk group. Further refinement of the 2022 ELN classification is warranted to address the unmet needs of patients with a very poor prognosis.
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