Topline Presentation Points 
Updates – Newly Diagnosed AML in older and/or unfit patients (0:25 – 6:10)


Real World Experience of CPX-351 as first-line treatment (Rautenberg et al. ASH 2021)
Builds 5-year study results of CPX-351 by Lancet, JCO 2020

Key Takeaways:

  • Promising CR rate of 47% and majority go onto transplant
    • CR rates significant across subgroups regardless of mutation status
  • Encouraging long term survival with 1 year CIR 23%

Limitations: Real world data and retrospective analysis


Comparing CPX-351 vs HMA+VEN (Grenet et al. ASH 2021)
Retrospective multicentre analysis of outcomes

Key Takeaways:

  • Significant survival advantage for CPX-351 in TP53 Mut
    • Greater transplant rate which may underline observed OS advantage
  • HMA+VEN has similar CR/CRi at 56.6% in this high-risk population

Limitations: Disparity in terms of age and high-risk cytogenetics which didn’t favour VEN+AZA arm


VEN+AZA vs intensive chemotherapy as induction (Zeidan et al. Blood 2021)
Retrospective analysis of an electronic database in the US

Key Takeaways:

  • OS similar in both treatment groups, regardless of age group and censoring patients with ASCT
    • 48% OS VEN+AZA in older population with high risk is quite encouraging
Update – Practice changing in Fit (6:10 – 7:35)


Updated results QUAZAR AML-001 Trial – long term OS with oral AZA in first remission after intensive chemotherapy
(Wei et al. ASH 2021)
Important update on practice changing study in fit patients

Key Takeaways:

  • Compelling OS benefit of maintenance with survival benefit maintained
    • Long term survivors more likely:
      • Intermediate-risk cytogenetics and NPM1 Mut at initial diagnosis
      • MRD negative by MFX at screening (post-IC)
  • Statistical improvement maintained across all subgroups
Update – Not fit for intensive chemo (7:35 – 10:56)


Phase I/II Study of AZA+VEN and Magrolimab
(Daver et al. ASH 2021 or Blood 2021)
Aims of study: Dose finding, signs of activity, and safety in newly diagnosed older/unfit or high risk and rrAML

Key Takeaways:

  • Preliminary data with encouraging signs:
    • Well tolerated
    • Complete Cytogenetic CR was achieved in 75% of evaluable patients
    • ORR in TP53 (86%) or wild type (100%)
    • Med TT ANC >500 28 days
    • Med TT Pit >50K 24 days

Limitations: Preliminary data with relatively small cohorts

TARGETABLE MUTATIONS (10:57- 18:57)

Phase 3 QuANTUM-First

Intensive ChemoRx +/- Quizartinib in newly diagnosed FLT3-ITD AML

  • Patients randomized to 3+7 chemoRx +/- QUIZ or Placebo
  • Post-chemoRx continue QUIZ for up to 3 years

Key Takeaways:

  • Primary end point of OS
  • Full data set at EHA 2022?


Phase 3 Gilteritinib+Aza vs Aza for newly diagnosed FLT3 Mut ineligible for intensive induction chemotherapy
(Wang et al. ASH 2021)
An open label randomized study

Key Takeaways:

  • Median time to first subsequent AML therapy was 8.2 mo for GIL+AZA and 4.5 mo for AZA
  • CR rates similar for both arms, CRc significantly higher for GIL+AZA

Limitation: Higher proportion of patients in AZA received subsequent AML therapy

Phase 1b Evaluating the safety and efficacy of VEN+GILT in rrAML (Daver, ASH 2021)
Multicentre, open label where 59% of patients had received >1 prior FLT3 TKI

Key Takeaways:

  • Encouraging data as VEN+GILT demonstrated deep reduction in FLT3 allelic burden with 74.5% patients achieving mCRc


AZA+VEN+GILT in FLT3 Mut
(Short, Blood 2021)

Key Takeaways

  • This triplet can be administered in upfront disease or rrAML
    • Frontline ORR 100%
    • Salvage ORR 69%


HMA+VEN with FLT3 inhibitor – “triplet” therapy in older/unfit patients with FLT3 Mut
(Yilmaz, Blood 2021)

Key Takeaways:

  • FLTi added to HMA+VEN appears to be safe and effective


Phase III AGILE Study – Ivosidenib+AZA vs Placebo+AZA in newly diagnosed with IDH1 Mut
(Montesinos et al. Blood 2021)
Unfit patients ineligible for intensive induction chemotherapy

Key Takeaways:

  • IVO+AZA significantly improved EFS and OS
  • Favourable safety profile – well tolerated, modest toxicity
  • Emerging combo in this patient population


Phase 1, First in human study of SNDX-5613
(Stein et al. ASH 2021)
Safety and efficacy of Menin Inhibition in patients with MLL-Rearranged and NPM1 mutant Acute Leukemia

  • SNDX-5613 turns off leukemic transcription programs by binding and to Menin and displacing MLL complexes

Key Takeaways:

  • SNDX-5613 patients are heavily pre-treated and have poor prognosis
  • SNDX-5613 demonstrates promising anti-Leukemia activity in rrMLLr and mNPM1 leukemias


Phase 1b/2 Study of IMGN632 combination AZA+VEN
(Daver et al. ASH 2021)
Treatment directed at patients with CD123-Positive AML

Key Takeaways:

  • Antileukemic activity observed across all doses/schedules
  • Manageable safety and efficacy
ALLOGENEIC TRANSPLANT (18:57 – 22:35)

ASCT remains a key modality in high-risk AML


Treatment and outcomes for Patients with TP53 Mut AML: Impact of ASCT on survival
(Badar et al. Blood 2021)
Clinical outcomes analyzed on 315 patients with TP53 Mut over last decade

Key Takeaways:

  • Allo-HCT as a time dependent covariate retained favourable prognostic significance in MVA

Allogeneic Hematopoietic Cell Transplant can overcome adverse prognosis of secondary-type mutation positive de novo AML (Song et al. Blood 2021)

Key Takeaways:

  • Benefit of allogeneic transplant
  • ASCT remains a key modality in high-risk AML