The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia
Abstract
:Simple Summary
Abstract
1. Introduction
Mutation | Type of Mutation | Reference | |
---|---|---|---|
Class I | FLT 3 (FLT3-ITD; FLT3-TKD) | FLT3- ITD, in-frame duplications of variable size, multiple copies of the gene in a row. FLT3- TKD, point mutations within the receptor’s activation loop, single change, or gene deletions | [8,11,15] |
K-RAS and N-RAS | Activated point mutations | [8,11] | |
TP53 | Missense substitutions (75%); Frameshift insertions and deletions (9%); non-sense mutations (7%); Silent mutations (5%), and other rare aberrations (2%). | [8,11,16] | |
c-Kit | Overexpression and point mutations | [8,11,17] | |
Class II | NPM1 | Frameshift insertions of usually 4-bp | [8,11,18] |
CEBPA | N-terminal frame-shift insertions/deletions and/or C-terminal in-frame insertions/deletions | [8,11,19] | |
Class III | DNMT3A | DNA methylation | [8,11] |
TET2 | |||
IDH-1 and IDH-2 |
2. Immune System in Acute Myeloid Leukemia
3. Acute Myeloid Leukemia Therapy
3.1. Chemotherapy
3.2. Allogeneic Stem Cell Transplantation
Graft-Versus-Leukemia Effect and Graft-Versus-Host Disease
3.3. Immunotherapy
3.3.1. Cytotoxic T Lymphocyte Antigen 4
3.3.2. Programmed Death-1 and Programmed Death-Ligand 1
4. Materials and Methods
5. Results
Study | Antigen Target | Therapy | Patients | Results | Ref. |
---|---|---|---|---|---|
Davids MS et al., 2016 | CTLA4 | Ipilimumab | 28 patients (12 AML) relapsed hematologic malignancies after allo-HSCT | GvHD in 14% of the patients; No response at 3 mg/kg; From 22 patients who received 10 mg/kg, 23% CR, and 27% decreased tumor burden; 5 of the 12 AML patients with CR, 4 having extramedullary AML. | [73] |
Reville K. Patrick et al., 2021 | PD-1 | Nivolumab | 15 patients with high-risk AML | 6-month RFS is 57.1% and median RFS is 8.48 months; | [75] |
Davids et al., 2020 | PD-1 | Nivolumab | 28 patients (10 AML) with relapsed hematologic malignancies, post- allo-HSCT | 3 early toxicities; 5 treated at 1 mg/kg/20 treated at 0.5 mg/kg; OS 56%. PFS 23%. | [76] |
Albring et al., 2017 | PD-1 | Nivolumab | 3 case studies in patients with relapsed AML after allo-SCT and failing standard therapy | 2 of the 3 patients, previously relapsed are in CR; the other patient was in molecular stabilization for 6 months. | [21] |
Ravandi et al., 2019 | PD-1 | Nivolumab + Idarubicin + Cytarabine | 44 patients with newly diagnosed AML and high-risk MDS | Median OS was 18 months; 6 patients with immune-related adverse events; 43% achieved response and proceeded to allo-HSCT. | [78] |
Oran B et al., 2020 | PD-1 CTLA-4 | Nivolumab Ipilimumab +Cytarabine +Idarubicin | 43 AML and MDS patients treated with checkpoint blockers before allo-HSCT | 34 with PD-1 blockade; 9 with CTLA-4 blockade; 24 patients CR, 6 patients CR with incomplete hematologic recovery; 5 patients showed hematologic improvement and 1 patient partial response. | [79] |
6. Discussion
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Medical Subject Headings Terms | AND | OR | NOT |
---|---|---|---|
Acute myeloid leukemia | Immune Checkpoint | ||
Acute myeloid leukemia | Treatment | ||
Acute myeloid leukemia | Treatment | PD-1/PD-L1 | CTLA-4 |
Acute myeloid leukemia | Treatment | CTLA-4 | PD-1/PD-L1 |
Acute myeloid leukemia | Treatment, PD-1/PD-L1, CTLA-4 |
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Silva, M.; Martins, D.; Mendes, F. The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia. Onco 2022, 2, 164-180. https://doi.org/10.3390/onco2030011
Silva M, Martins D, Mendes F. The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia. Onco. 2022; 2(3):164-180. https://doi.org/10.3390/onco2030011
Chicago/Turabian StyleSilva, Margarida, Diana Martins, and Fernando Mendes. 2022. "The Role of Immune Checkpoint Blockade in Acute Myeloid Leukemia" Onco 2, no. 3: 164-180. https://doi.org/10.3390/onco2030011