Table 1.
Data from frontline, prospective studies on FLT3-mutated AML in older adults.
| Study | FLT3 mutation status | Treatment regimen | N | Clinical activity | Study notes |
|---|---|---|---|---|---|
| Intensive Chemotherapy + FLT3 inhibitor | |||||
| Sierra J et al. 2020 [61] | ITD and TKD |
7 + 3 plus midostaurin or 5 + 2 plus midostuarin |
142 | CR/CRi: 78% | • Subgroup analysis of age >60 cohort |
| Dohner H et al. 2022 [39] | ITD only | 7 + 3 plus midostaurin | 128 |
CR/CRi: 72% EFS: 11.7 months Median OS: 22.7 months |
• Subgroup analysis of age 61–70 cohort |
| Erba H et al. 2023 [37] | ITD only |
7 + 3 plus quizartinib vs 7 + 3 plus placebo |
216 |
Quizartinib (n = 107): Median OS 17.5 months Placebo (n = 109): Median OS 14.2 months |
• Subgroup analysis of age >60 cohort |
| Lower-Intensity Doublet with FLT3 Inhibitor | |||||
| Swaminathan M et al. 2021 [42] | ITD only |
Azacitidine + quizartinib or LDAC + quizartinib |
34 |
CRc: 79% Median RFS: 8.0 months Median OS: 12.4 months |
• Decision to use azacitidine or LDAC based on clinician’s choice |
| Dennis M et al. 2021 [43] | ITD only |
LDAC alone vs LDAC + quizartinib |
27 |
LDAC alone (n = 14): CRc: 0% Median OS: 4.2 months LDAC/Quiz (n = 13): CRc: 38% Median OS: 13.7 months |
• Enrolled patients irrespective of FLT3 status; data are subgroup analysis of FLT3-ITD cohort |
| Ohanian M et al. 2018 [41] | ITD only | Azacitidine + sorafenib | 27 |
ORR: 78% Median DoR: 14.5 months Median OS: 8.3 months |
|
| Wang ES et al. 2022 [45] |
ITD (n = 98), TKD (n = 21), Co-mutation (n = 4) |
Azacitidine alone vs Azacitidine + gilteritinib |
123 |
Aza alone (n = 49): CRc: 26.5% Median OS: 8.87 months Aza/Gilt (n = 74): CRc: 58.1% Median OS: 9.82 months |
|
| Lower-Intensity Triplet with FLT3 Inhibitor | |||||
| Maiti A et al. 2021 [56] |
ITD (n = 8), TKD (n = 3), Co-mutation (n = 1) |
Decitabine + venetoclax + FLT3i of choice [gilteritinib, n = 5 sorafenib, n = 5 midostaurin, n = 2] |
12 |
CRc: 92% Median OS: Not reached 2-year OS: 80% |
• Decision for FLT3 inhibitor per clinician’s choice |
| Yilmaz M et al. 2022 [57] | ITD only | Decitabine + venetoclax + quizartinib | 6 |
CR/CRi: 100% Median OS: 14.5 months |
|
| Short NJ et al. 2022 [58] |
ITD (n = 22), TKD (n = 8) |
Azacitidine + venetoclax + gilteritinib | 30 |
CR/CRi: 100%; CR: 90% Median OS: Not reached 2-year OS: 71% |
|
ITD internal tandem duplication, TKD tyrosine kinase domain, LDAC low-dose cytarabine, CR complete remission, CRi complete remission with incomplete hematologic recovery, CRc composite CR rate, EFS event-free survival, DoR duration of response, RFS relapse-free survival, OS overall survival.