Table 3.
Summary of relevant clinical trials with targeted agents in AML.
| Substance Group | Agent | Target | Ph | Patient Cohort | Schedule | ORR (%) | PFS (m) | OS (m) | A |
|---|---|---|---|---|---|---|---|---|---|
| FLT 3 Inhibitors | Midostaurin [61,62,63] | FLT3 (non mutated) | I | R/R or unfit | + AZA | 21 | NR | 6 | Y |
| FLT 3 mutated or WT | I | De novo | + CTx | 80 | NR | NR | |||
| FLT3 mutated or WT | II | R/R or unfit | M | 71 (mutated) 42 (WT) | NR | 4.3 | |||
| FLT3 mutated | III | De novo | + CTx | 59/53 | 26.7/15.5 | 74.7/25.6 | |||
| Quizartinib [64,65,66,67] | FLT3 mutated | I | R/R | M | 30 | NR | 3.5 | Y | |
| FLT3 mutated or WT | II | R/R | M | 47 | 2.2 | 6.7 | |||
| FLT3 mutated or WT | II | R/R | M | 74–77 | 3 | 6 | |||
| FLT3 mutated | III | R/R | M vs. CTx | 48 vs. 27 | 4 vs. 1.2 | 6.2 vs. 4.7 | |||
| Gilteritinib [68] | FLT3 (mutated) | I | R/R | M | 40 | 4.25 | 6.25 | Y | |
| Lestaurtinib [69] | FLT3 (mutated) | III | De novo | + CTx | 97 | 40 vs. 36% (NS) | 5 y OS 46 vs. 45% (NS) | N | |
| Sunitinib [70] | FLT 3 (mutated) | I/II | De novo elderly | + CTx | 59 | 12 | 18 | N | |
| Crenolanib [71,72,73,74,75] | FLT ITD and D835 | II | De novo | + CTx | 96 | NR | Nre | N | |
| II | De novo | + CTx | 83 | NR | Nre | ||||
| II | R/R | + CTx | 67 | NR | NR | ||||
| II | R/R | + CTx | 36 | NR | 9.25 | ||||
| II | R/R | M | 47 | 2 | 4.75 | ||||
|
Sorafenib [76,77,78,79,80,81] |
Multiple kinases | II | De novo | + CTx | 60 vs. 59 | 9 vs. 21 | Nre | N | |
| I | R/R | M | 10 | NR | NR | ||||
| I | After AlloTx in FLT3-ITD | M | NR | 85% at 12 Mo | 95% at 12 Mo | ||||
| I | R/R after AlloTx with FLT3-ITD |
+ AZA | 50 | NR | 322 days | ||||
| III | Maintenance After alloTx |
M | NR | Nre vs. 30.9 | NR | ||||
| IDH Inhibitors | Enasidenib [82] | IDH 2 (mutated) | I/II | R/R | M | 40 | 6.4 | 9.3 | Y |
| Ivosidenib [83] | IDH 1 (mutated) | I | R/R | M | 41 | NR | NR | Y | |
| Bcl-2 Inhibitors |
Venetoclax [84,85] |
Bcl-2 | II | R/R or unfit | M | 19 | 2.5 | 4.7 | Y |
| Ib | unfit | + AZA or DAC | 73 | NR | 18 | ||||
| Obatoclax [86] | Bcl-2 family | I/II | unfit | M | 0 | NR | NR | N |
R/R: relapsed or refratory, unfit: patient unfit for intensive chemotherapy, PFS: progression free survival, OS: overall survival, NR: not reported, M: monotherapy, +CTx: in combination with high dose chemotherapy, A: approved, Y: yes, N: No, Nre: not reached, HDAC: histone deacetylase; AZA: azacytidine, FLT3: fms like tyrosine kinase 3, WT: wild type, AlloTx: allogeneic bone marrow transplantation, ITD: internal tandem duplication, DAC: decitabine; Substances are ordered by substance class in order of approval date. Within the subgroups, approved substances are listed first.