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Immune checkpoint inhibitors (ICIs) in acute myeloid leukemia (AML) therapy are being evaluated in a variety of clinical trials. Unfortunately, significant differences in response rate have been observed amongst clinical trials using ICIs, probably because of different immune checkpoint (IC) expression levels or expression patterns that yet need to be fully characterized.
Here we report the results of a study recently published in the Journal of Hematology & Oncology by Cunte Chen et al., evaluating the IC expression patterns and its prognostic value in patients with newly diagnosed or de novo AML.1
The use of ICIs in AML therapy is the current AML Hub editorial theme, read more information here.
Table 1. 3-year OS in AML patients with high or low PD-1, PD-L1, or PD-L2 expression1
OS, overall survival |
||
|
3-year OS, % |
p value |
---|---|---|
TCGA group (n = 176) PD-1 High Low PD-L1 High Low PD-L2 High Low |
23 38
19 46
15 40 |
0.004
0.019
0.001 |
Validation group (n = 62) PD-1 High Low PD-L1 High Low PD-L2 High Low |
40 68
22 64
42 68 |
0.020
< 0.001
0.012 |
Table 2. 3-year OS in patients with high expression of PD-1, PD-L1 or PD-L2 concomitant with CTLA-4low or CTLA-4high
CTLA-4, cytotoxic T-lymphocyte associated protein 4; OS, overall survival *Value indicated in bold is not statistically significant |
||
|
3-year OS, % |
p value |
---|---|---|
TCGA group PD-1high CTLA-4low CTLA-4high PD-L1high CTLA-4low CTLA-4high PD-L2high CTLA-4low CTLA-4high |
30 0
24 0
20 0 |
0.036
< 0.001
0.041 |
Validation group PD-1high CTLA-4low CTLA-4high PD-L1high CTLA-4low CTLA-4high PD-L2high CTLA-4low CTLA-4high |
57 31
33 20
57 33 |
0.042
0.353
0.043 |
Table 3. 1-year OS in patients with FLT3, RUNX1, or TET2 mutations and co-expressions of PD-1, PD-L1, PD-L2 or LAG-31
LAG-3, lymphocyte activation gene-3; OS, overall survival |
||
|
1-year OS, % |
p value |
---|---|---|
FLT3mut PD-1high/PD-L1high PD-1high or PD-L1high PD-1low/PD-L1low |
0 58 49 |
0.029 |
RUNX1mut PD-1high/PD-L1high/PD-L2high PD-1high or PD-L1high or PD-L2high PD-1low/PD-L1low/PD-L2low |
0 56 100 |
0.003 |
TET2 mut PD-1high/LAG-3high PD-1high or LAG-3high PD-1low/LAG-3low |
0 100 63 |
< 0.001 |
This study showed that patients with AML and high expression of PD-1, PD-L1, or PD-L2 have significantly shorter survival. Moreover, the correlation between higher expression of the named ICs with CTLA-4 and LAG-3 gives the biological rationale to test dual-targeted combinations of ICs in these patients.
Furthermore, the co-expression of PD-1/ CTLA-4 or PD-L2/CTLA-4 was associated with poorer OS in patients with de novo AML. In addition, the concomitant high expression of PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 was associated with poor OS in patients with FLT3, RUNX1, or TET2 mutations, respectively. This co-expression patterns might be potential biomarkers for designing novel AML targeted therapy and need to be further explored. Altogether, these results demonstrated that high expression of ICs correlated with poor outcome in patients with de novo AML, highlighting their potential prognostic value.
References
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