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)
- Long term survivors more likely:
- 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
