Key factors for the development of a potential personalized medicine approach60
| Variable . | Entity . | Grading . | Potential clinical consequence . |
|---|---|---|---|
| Performance status | ECOG 0-1 | Good | Standard therapy including allo-HCT |
| ECOG >1 | Poor | Supportive care or low-intensity therapy | |
| EPO level | <200 U/L | Low | Treatment with ESA in case of anemia |
| >200 U/L | High | No ESA (limited response to ESA) | |
| Ferritin level | >1500 ng/mL | High | Treatment with iron chelation* |
| Genetics | del(5q) | Targeted treatment with lenalidomide* | |
| Normal karyotype, 20q-, -Y: and absence of poor-risk molecular abnormalities | Good risk | Standard therapy or supportive care only | |
| All other aberrations, including complex karyotype, or poor-risk molecular abnormalities | Poor risk | Intensified surveillance strategy, allo-HCT, clinical trial | |
| Druggable molecular targets | SF3B1 mutation | Treatment with luspatercept* | |
| TP53 mutation | Treatment with TP53 modulators | ||
| TP53 WT | Treatment with Nutlins | ||
| IDH1 mutation | Treatment with IDH1 inhibitors | ||
| IDH2 mutation | Treatment with IDH2 inhibitors | ||
| Spliceosome mutations | Treatment with spliceosome modulators | ||
| Prognostic scoring systems (eg, IPSS-R) | IPSS-R score ≤3.5 | Good risk | Standard therapy or supportive care only |
| IPSS score >3.5 | Poor risk | Hypomethylating agents,* allo-HCT | |
| Inflammatory signature | Yes | Anti-inflammatory treatment | |
| No | Standard therapy |
| Variable . | Entity . | Grading . | Potential clinical consequence . |
|---|---|---|---|
| Performance status | ECOG 0-1 | Good | Standard therapy including allo-HCT |
| ECOG >1 | Poor | Supportive care or low-intensity therapy | |
| EPO level | <200 U/L | Low | Treatment with ESA in case of anemia |
| >200 U/L | High | No ESA (limited response to ESA) | |
| Ferritin level | >1500 ng/mL | High | Treatment with iron chelation* |
| Genetics | del(5q) | Targeted treatment with lenalidomide* | |
| Normal karyotype, 20q-, -Y: and absence of poor-risk molecular abnormalities | Good risk | Standard therapy or supportive care only | |
| All other aberrations, including complex karyotype, or poor-risk molecular abnormalities | Poor risk | Intensified surveillance strategy, allo-HCT, clinical trial | |
| Druggable molecular targets | SF3B1 mutation | Treatment with luspatercept* | |
| TP53 mutation | Treatment with TP53 modulators | ||
| TP53 WT | Treatment with Nutlins | ||
| IDH1 mutation | Treatment with IDH1 inhibitors | ||
| IDH2 mutation | Treatment with IDH2 inhibitors | ||
| Spliceosome mutations | Treatment with spliceosome modulators | ||
| Prognostic scoring systems (eg, IPSS-R) | IPSS-R score ≤3.5 | Good risk | Standard therapy or supportive care only |
| IPSS score >3.5 | Poor risk | Hypomethylating agents,* allo-HCT | |
| Inflammatory signature | Yes | Anti-inflammatory treatment | |
| No | Standard therapy |
ECOG, Eastern Cooperative Oncology Group; EPO, erythropoietin; WT, wild type.
FDA approved