Table 2.
New therapeutics in pediatric AML
| Drug | Mechanism of action | Current stage of development in pediatric AML |
|---|---|---|
| Drug-antibody conjugates | ||
| Gemtuzumab ozogamicin [14] | Anti-CD33 antibody with calicheamicin payload |
FDA-approved for newly diagnosed AML > 1 month of age Standard of care as single dose in induction 1 |
| Flotetuzumab [58] | CD123/CD3 bispecific dual-affinity retargeting antibody | Phase I trials for r/r AML |
| Nivolumab [61] | Anti-PD-1 antibody/checkpoint inhibitor | Phase I/II trial for r/r AML combined with azacitidine |
| Epigenetic modifiers | ||
| Decitabine [67] | Hypomethylating agent: inhibits DNA methyltransferases |
Completed phase I trial for r/r AML Phase II trial with standard chemotherapy in newly diagnosed AML |
| Azacitidine [68] | Hypomethylating agent: inhibits DNA methyltransferases |
Phase I/II trials for r/r AML Phase II trial with standard chemotherapy in newly diagnosed AML |
| Vorinostat [72] | Inhibits histone deacetylase | Phase I trial for r/r AML |
| Panobinostat [71] | Inhibits histone deacetylase | Phase I trial for r/r AML |
| Tyrosine kinase/FLT3 inhibitors | ||
| Sorafenib [80] | 1st-generation type II TKI: active against FLT3-ITD and FLT3-TKD mutations | Completed phase III trials for high AR FLT3-ITD AML |
| Midostaurin [83] | 1st-generation type I TKI: active against FLT3 and KIT mutations |
USA: phase I/II trials terminated for low enrollment International: ongoing phase II trial |
| Gilteritinib [87] | 2nd-generation type I TKI: active against FLT3 and AXL |
Phase III trials combined with standard chemo in newly diagnosed AML Phase I/II trial combined with FLAG for r/r AML |
| Quizartinib [75] | Type II TKI | Phase I/II trials in r/r AML |
| Crenolanib [75] | Type I TKI | Completed phase I trial in r/r leukemias |
| Others | ||
| Venetoclax [99] | Inhibits BCL-2 | Phase I/II trials for r/r AML |
| CPX-351 [99] | Liposomal formulation of daunorubicin and cytarabine—enhances synergy between drugs and extends half-life |
Completed phase I/II trials for r/r AML Current phase III trial for newly diagnosed AML |
| Atovaquone [99] | Inhibits oxidative phosphorylation and STAT3 activation | Phase I trial with standard chemotherapy |
| Chimeric antigen receptor T cells | ||
| CD123-targeting CAR-T [62] | T cells genetically modified to target/kill CD123-expressing AML cells | Phase I trials for r/r AML |
| CD33-targeting CAR-T [46] | T cells genetically modified to target/kill CD33-expressing AML cells | Phase I trials for r/r AML |
FDA, Food and Drug Administration; r/r, relapsed/refractory; TKI, tyrosine kinase inhibitor; ITD, internal tandem duplication; TKD, tyrosine kinase domain; AR, allelic ratio; FLAG, fludarabine, cytarabine, granulocyte colony-stimulating factor; CAR-T, chimeric antigen receptor T cell