Table 2 Published studies of approved and investigational uses of FDA-approved and/or NCCN-recommended targeted therapies in AML
From: Recent advances in targeted therapies in acute myeloid leukemia
Targeted therapy | AML study indication (Ref.) | Study arms | Median age (years) | N | CR (%) | CRc (definition, %) | mOS (months) | Final dose/schedule in study | FDA-approved use | NCCN-recommended use |
|---|---|---|---|---|---|---|---|---|---|---|
IVO | R/R [87] | IVO, single arm | 67 | 125 | 21.6 | CR/CRh, 30.4 | 8.8 | 500 mg daily | 1. Frontline monotherapy for ND IDH1-AML if ≥ 75 years or unfit for IC 2. Frontline IVO/AZA for ND IDH1-AML if ≥ 75 years or unfit for IC 2. Monotherapy for R/R IDH1-AML | 1. Frontline monotherapy for IDH1-AML if ≥ 60 years and unfit for IC 2. Frontline IVO/AZA for IDH1-AML if ≥ 60 years old and unfit for IC 3. Maintenance monotherapy after low-intensity induction for IDH1-AML 4. Monotherapy for R/R IDH1-AML |
ND [88] | IVO, single arm | 76.5 | 34 | 30.3 | CR/CRh, 42.4 | 12.6 | ||||
ND [93] | IC/IVO, single arm | 62.5 | 60 | 68.3 | CR/CRi/CRp, 76.7 | NR Estimated 12-month OS 78% | 500 mg daily starting day 1 of IC ± consolidation ± maintenance | |||
ND [97] | AZA/IVO | 76 | 23 | 60.9 | CR/CRi/CRp, 69.6 | NR Estimated 12-month OS 82.0% | IVO 500 mg daily (day 1–28) AZA 75 mg/m2 daily (day 1–7) | |||
ND [98] | AZA/IVO vs. AZA/PBO | 76 vs. 75.5 | 72 vs. 74 | 47.2 vs. 14.9 | CR/CRi/CRp, 54.2 vs. 16.2 | 24.0 vs. 7.9 | ||||
OLU | R/R [91] | OLU vs. AZA/OLU | 72 vs. 67 | 22 vs. 26 | 18 vs. 12 | CR/CRp, 32 vs. 15 | 8.7 vs. 12.1 | OLU 150 mg twice daily AZA 75 mg/m2 daily (day 1–7) | 1. Monotherapy for IDH1-AML | None |
ND [91] | OLU vs. AZA/OLU | 72 vs. 67 | 4 vs. 13 | 0 vs. 54 | CR/CRp, 0 vs. 54 | 8.8 vs. NR | ||||
ENA | ENA, single arm | 68 | 214 | 19.6 | CR/CRi/CRp, 29.0 | 8.8 | 100 mg daily | 1. Monotherapy for R/R IDH2-AML | 1. Frontline monotherapy for IDH2-AML if ≥ 60 years and unfit for IC 2. Maintenance monotherapy after low-intensity induction for IDH2-AML 3. Monotherapy for R/R IDH2-AML | |
R/R [85] | ENA vs. Conventional care | 72 vs. 71 | 158 vs. 161 | 23.4 vs. 3.7 | CR/CRi/CRp, 29.7 vs. 6.2 | 6.5 vs. 6.2 | ||||
R/R [100] | AZA/ENA, single arm | 64 | 19 | 27.7 | CR/CRi, 61.1 | Not reported Estimated 12-month OS if treated in 1st relapse 75% vs. ≥ 2nd relapse 10% | ENA 100 mg daily (day 1–28) AZA 75 mg/m2 daily (day 1–7) | |||
ND [86] | ENA, single arm | 77 | 39 | 17.9 | CR/CRi/CRp, 20.5 | 11.3 | 100Â mg daily | |||
ND [93] | IC/ENA, single arm | 63 | 93 | 54.9 | CR/CRi/CRp, 73.6 | 25.6 | 100Â mg daily starting day 1 or day 8 of IC | |||
ND [101] | AZA/ENA vs. AZA/PBO | 75 vs. 75 | 68 vs. 33 | 54.4 vs. 12.1 | CR/CRi/CRp, 63.2 vs. 30.3 | 22.0/22.3 | ENA 100 mg daily (day 1–28) AZA 75 mg/m2 daily (day 1–7) | |||
ND [100] | AZA/ENA, single arm | 77 | 7 | 71.4 | CR/CRi, 100 | NR Estimated 12-month OS for ND group was 83% | ||||
MIDO | ND [114] | IC/MIDO, single arm | Total (48.5) FLT3 mutant [46] | Total [40] FLT3 mutant [13] | Total [80] FLT3 mutant [92] | Not reported | Not reported Estimated 12-month OS for FLT3-mutant 85% | 50 mg BID on days 1–7 and days 14–21 (concomitant) or days 8–21 (sequential) of IC ± consolidation ± maintenance | 1. MIDO + IC, re-induction, and consolidation for FLT3-TKD or ITD AML if eligible for IC | 1. MIDO + IC, re-induction, and consolidation for FLT3-TKD or ITD AML if eligible for IC and with intermediate/poor-risk cytogenetics |
ND [118] | IC/MIDO vs. IC | 47.1 vs. 48.6 | 360 vs. 357 | 58.9 vs. 53.5 | Not reported | 74.7 vs. 25.6 | 50 mg BID on days 8–21 of IC ± consolidation ± maintenance | |||
IC/MIDO, single arm | 54.1 | 440 | 37 | CR/CRi, 74.9 | 36.2 | 50 mg BID on days 8 of IC continuously until 48 h prior to next cycle ± consolidation ± maintenance |  |  | ||
GILT | R/R [117] | GILT vs. Conventional care | 62.0 vs. 61.5 | 247 vs. 124 | 21.1 vs. 10.5 | CR/CRi/CRp, 54.3 vs. 24.8 | 9.3 vs. 5.6 | 120Â mg daily | 1. GILT monotherapy for R/R FLT3-TKD or ITD AML | 1. GILT monotherapy for R/R FLT3-TKD or ITD AML |
R/R [135] | VEN/GILT, single arm | 63 | 56 | 18 | CR/CRi/CRp, 39 | 10.0 | GILT 120Â mg daily VEN 400Â mg daily | |||
SORA | R/R [130] | AZA/SORA, single arm | 64 | 43 | 16 | CR/CRi, 43 | 6.2 | SORA 400 mg BID (days 1–28) AZA 75 mg/m2 daily (day 1–7) | None | 1. SORA  + AZA or DAC + for R/R FLT3-ITD AML 2. Frontline SORA + AZA or DAC for FLT3-ITD AML if unfit for IC 3. SORA + AZA or DAC + SORA maintenance after low-intensity induction for FLT3-ITD AML 4. SORA maintenance after alloHSCT in FLT3-ITD AML |
ND [136] | AZA/SORA, single arm | 74 | 27 | 26 | CR/CRi/CRp, 70 | 8.3 | ||||
IC/SORA vs. IC | 50 vs. 50 | 134 vs. 133 | 60 vs. 59 | Not reported | NR vs. NR 5-year OS 61% vs. 53% | 400 mg BID on days 10–19 of IC ± consolidation ± maintenance | ||||
MAIN [146] | SORA vs PBO | 54.2 vs. 53.6 | 43 vs. 40 | N/a | N/a | NR vs. NR Estimated 2-year OS 90.5% vs. 66.2% | 400Â mg BID | |||
MAIN [148] | SORA vs PBO | 35 vs. 35 | 100 vs. 102 | N/a | N/a | NR vs. NR Estimated 2-year OS 82.1 vs. 68.0 |