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Positive outcomes reported in patients with core-binding factor (CBF) fusions such as t(8;21)(q22;q22) or inv(16) (p13.1q22)/t(16;16) (p13.1;q22) have led to the creation of a distinct molecular subclass of acute myeloid leukemia (AML) by the World Health Organization (WHO). Moreover, CBF-AML is classified as ‘favorable risk’ by both the European LeukemiaNet guidelines and the National Comprehensive Cancer Network. Research indicates that there may not be any survival benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) over chemotherapy in patients with CBF-AML in first complete remission (CR1); however, the impact of FLT3-internal tandem duplication (ITD) mutations, which occur in up to 10% of patients, has not been fully investigated.1
In a recent multicenter study published by Kayser et al.1 in Haematologica, patients with FLT3-ITD CBF-AML were characterized and treatment outcomes were compared, particularly with respect to allo-HSCT. We summarize key findings below.
This large, multicenter study investigated case reports from patients with CBF-AML and FLT3-ITD mutations from 1996 to 2019 across eight study groups/institutions in the US and Europe (Figure 1).
Figure 1. Study design*
AZA, azacitidine; CBF-AML, core-binding factor acute myeloid leukemia; CID, cumulative incidence of death in complete remission; CIR, cumulative incidence of relapse; OS, overall survival; RFS, relapse-free survival.
*Adapted from Kayser et al.1
Patient characteristics are summarized in Table 1.
Table 1. Patient characteristics*
Characteristic |
N = 97 |
---|---|
Median age, years (range) |
53 (19–81) |
Female, % |
46 |
Median WBC, × 109/L (range) |
20.5 (1.8–298) |
Median Hb, g/dL (range) |
8.6 (4.6–14.3) |
Median platelet count, × 109/L |
33 (7–372) |
Median BM blasts, % (range) |
60 (0–98) |
Cytogenetics, % |
|
CBF as sole abnormality |
42 |
CBF + other abnormality |
58 |
Trisomy 22 |
12 |
Trisomy 8 |
7 |
Disease type, % |
|
De novo AML |
90 |
Secondary AML |
2 |
Therapy-related AML |
8 |
Median FLT3-ITD allelic ratio (range) |
0.35 (0.003–50) |
FLT3-TKD, % |
21 |
AML, acute myeloid leukemia; BM, bone marrow; CBF, core-binding factor; Hb, hemoglobin; ITD, internal tandem duplication; TKD, tyrosine kinase domain; WBC, white blood cell. |
Figure 2. 4-year RFS for patients with trisomy 22 with inv(16) and patients with other CBF-AML subtypes*
CBF-AML, core-binding factor acute myeloid leukemia.
*Data from Kayser et al.1
Results from the study1 demonstrate that patients with CBF-AML respond well to intensive chemotherapy, with high rates of CR irrespective of concurrent FLT3-ITD mutations. However, based on previously published data, patients with FLT3-ITD CBF-AML, excluding inv(16) with trisomy 22, demonstrated inferior outcomes compared to those with wildtype FLT3-ITD. The authors highlighted the 4-year OS rate of 51% observed in patients with FLT3-ITD CBF-AML who received intensive treatment, and compared this result to the 10-year OS rate of 58% reported in a previous study,2 conducted in patients with CBF-AML without the FLT3-ITD mutation. Thus, Kayser et al.1 recommend that the subgroup of patients with CBF-AML and FLT3-ITD should not be classified as ‘favorable risk’.
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