Acute Myeloid Leukemia: Treatment

Acute Myeloid Leukemia: overview

This algorithm organizes acute myeloid leukemia treatment by subtype, fitness for intensive therapy and disease phase. Acute promyelocytic leukemia (PML::RARA) is separated first: non-high-risk APL is treated with ATRA plus arsenic trioxide (APL0406), and high-risk APL (WBC above 10k) with ATRA plus arsenic trioxide with or without chemotherapy. For fit patients receiving intensive induction, the chart adds midostaurin to 7+3 for FLT3-mutated disease (RATIFY), gemtuzumab ozogamicin to 7+3 for CD33-positive disease (ALFA-0701), and uses CPX-351 for secondary AML.

For patients unfit for intensive therapy, azacitidine plus venetoclax is the standard (VIALE-A), which improved OS over azacitidine alone. IDH1-mutated disease may receive ivosidenib with or without azacitidine (AGILE), and IDH2-mutated disease enasidenib. In the post-remission and relapsed setting, allogeneic transplant is the curative option for intermediate or adverse risk disease, oral azacitidine is used as maintenance (QUAZAR), and gilteritinib is shown for FLT3-mutated relapse (ADMIRAL).

Trials behind this algorithm

APL0406 Lo-Coco Trial, ATRA+ATO Lo-Coco F et al, NEJM, 2013; PMID: 23841729
RATIFY/CALGB 10603 trial Stone RM et al, NEJM, 2017; PMID: 28644114
ALFA-0701 Castaigne S et al, Lancet, 2012; PMID: 22482940
CPX-351 in sAML Lancet EJ et al, JCO, 2018, PMID: 30024784
VIALE-A DiNardo CD et al, NEJM, 2020; PMID: 32786187
AGILE Montesinos P et al, NEJM, 2022; PMID: 35443108
Enasidenib R/R AML (phase 1/2) Stein EM et al, Blood, 2017; PMID: 28588020
QUAZAR trial, Aza maintenance Wei et al, NEJM, 2020, PMID: 33369355
ADMIRAL trial, gilteritinib in rrAML FLT3-ITD Perl AE et al, NEJM, 2019, PMID:31665578

Background reading: AML (Part 1): Biology, Diagnosis, Classification and Risk board review notes.

Acute Myeloid Leukemia: the algorithm in words

Starting point: Acute myeloid leukemia (AML). Full background: AML (Part 1): Biology, Diagnosis, Classification and Risk notes.

APL (PML::RARA) (first-line): Non-high-risk: ATRA + arsenic trioxide (APL0406); High-risk: ATRA + ATO ± chemo (WBC > 10k).
Fit: intensive induction (first-line): FLT3: 7+3 + midostaurin (RATIFY); CD33: 7+3 + gemtuzumab (ALFA-0701); sAML: CPX-351 (Vyxeos).
Unfit: lower-intensity (first-line): Azacitidine + venetoclax (VIALE-A); IDH1: Ivosidenib ± azacitidine (AGILE); IDH2: Enasidenib (IDH2-mutated).
Post-remission / relapsed (second-line): Curative: Allogeneic transplant (intermediate / adverse risk); Maintenance: Oral azacitidine (QUAZAR); FLT3: Gilteritinib (ADMIRAL).