Table 2 Molecular target therapeutic agents
From: Clinical implications of recurrent gene mutations in acute myeloid leukemia
Target | Types | Agents | Clinical efficacy |
|---|---|---|---|
FLT3 inhibitors | Type 1 | Midostaurin | 4-year OS 51.4% on midostaurin versus 44.2% on placebo on FLT3+ AML [37] EFS and OS at 2Â years were 39% and 34% in younger and 53% and 46% in older patients, respectively [38] Recommended as front line therapy for AML with FLT3-ITD and FLT3-TKD [9, 39] |
Sunitinib | Some promising results in phase I/II clinical trials, but with high incidence of adverse effects [40, 41] | ||
Gilteritiniba | R/R FLT3-mutated AML, median OS for single agent gilteritinib was significantly longer than chemotherapy (9.3Â months vs. 5.6Â months). Median EFS was 2.8Â months in the gilteritinib group and 0.7Â months in chemotherapy group [42] Recommended as new standard therapy for R/R FLT3-mutated AML [43] | ||
Lestaurtinib | Failed to demonstrate any overall clinical benefit in a phase III trial when combined with intensive chemotherapy in patients with newly diagnosed FLT3-ITD-mutated AML [9, 44, 45] | ||
Crenolaniba | Combine with 7 + 3 regimen can overcome the poor prognostic implication of adverse mutations co-occurring with mutated FLT3 [46] Incorporation of crenolanib into frontline intensive chemotherapy resulted high ORR and may replace Midostaurin in the upfront setting [47] | ||
Type 2 | Quizartiniba | Showed efficacy in multiple clinical trials in R/R AML with FLT3-ITD mutation [48,49,50] Recommended for patients with rapidly proliferative disease and very poor prognosis [51] | |
Sorafenib | Combine with intensive chemotherapy improves OS in newly diagnosed, FLT3-ITD mutated AML regardless allogeneic HSCT [52] Improved OS for FLT3-ITD AML relapsing after allo-HSCT [53] | ||
IDH inhibitors | IDH1 | Ivosidenib | 9/14 IDH1 mutation AML achieved CR + CRh (5/10 CR, 4/4 CRh) [85] Substantial efficacy with a small group study (n = 12) [86] |
IDH2 | Enasidenib | ORR 38% in R/R AML [87] ORR 30.8% in older adults AML with IDH mutation. Median OS was 11.3Â months [87] Benefit older adults with newly diagnosed IDH2-mutant AML who are not candidates for cytotoxic regimens [88] Fatal adverse effects including indirect hyperbilirubinemia and cytokine storm [89, 90] | |
IDH1 | Olutasidenib | Single agent ORR of 41% and combine with azacitidine ORR of 46% Induced deep responses with IDH1 mutation clearance [91] |