Topline Presentation Points 

Targeted Therapies and precision medicine

ASH abstract 871. Long-Term Overall Survival (OS) with Oral Azacitidine (Oral-AZA) in Patients with Acute Myeloid Leukemia (AML) in First Remission after Intensive Chemotherapy (IC): Updated Results from the Phase 3 QUAZAR AML-001 Trial
Andrew H. Wei et al.

Background

  • AML patients not eligible for transplant after intensive chemotherapy relapse (~80%) and have poor OS. QUAZAR AML-001 trial assessed Oral-AZA (CC-486) in transplant in-eligible pts with AML in remission after IC.

Conclusions

  • No change in median OS in QUAZAR AML-001
  • But KM -OS curves showed greater separation at later time-points than in the primary analysis indicating a sustained, long-term OS benefit with Oral-AZA.
  • Intermediate-risk cytogenetics and NPM1 mutations at AML Dx, and absence of detectable MRD post-IC, were associated with long-term survival in QUAZAR AML-001.

ASH abstract 798. Hypomethylating Agent (HMA) Therapy and Venetoclax (VEN) with FLT3 Inhibitor “Triplet” Therapy Is Highly Active in Older/Unfit Patients with FLT3 Mutated AML
Musa Yilmaz et al.

Background

  • FLT3 mutations are associated with a high risk of relapse and an inferior OS.
  • FLT3i + LIC or FLT3i +Ven : Expected median OS 8 to 12 months

Ohanian et al. AJH, 2018; Konopleva et. al. ASH, 2020

Conclusions

  • First- and second-generation FLT3i-based doublet regimens were associated with comparable response rates and survival of 9-16 months in older adults with newly diagnosed FLT3 mutated AML.
  • The HMA-VEN-FLT3i combination significantly improved CR/CRi rates, FLT3-PCR and MFC MRD rates as well as OS
  • No increase in early mortality
  • These findings suggest the need for prospective validation of HMA-VEN-FLT3i triplets in older/unfit AML.
Combinations of Targeted Therapies

ASH abstract 691. Venetoclax in Combination with Gilteritinib Demonstrates Molecular Clearance of FLT3 mutation in Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
Naval Daver et al.

Background

  • FLT3i + Ven have shown lethality in preclinical models which may prevent or delay drug resistance

Additional Presenter Perspective: Clinicians see a lot of drug resistance and poor long-term survival with FLT 3 mutated disease

Conclusions

  • Ven + Gilt achieved high mCRc in patients with R/R FLT3+ AML, with or without prior TKI exposure, and an encouraging mOS.
  • FLT3 mutation clearance was seen in majority of patients and associated with longer OS.
  • High remission rates were observed among pts with NPM1⁺ +/- DNMT3A co-mutation
  • Cytopenias were common but manageable with appropriate Ven or Gilt dosing modifications

ASH abstract 693. Intensified Cytarabine Dose during Consolidation Therapy in AML Patients Under 65 Years Is Not Associated with Survival Benefit
Maher Hanoun et al.

Additional Presenter Perspective: This study looked to address the ‘age old question’ of optimal dosing with cytarabine consolidation’

Background

  • Retrospective analysis from the German Study Alliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry

Conclusions

  • This retrospective analysis suggests no significant benefit of high dose cytarabine compared to intermediate dosages in consolidation for AML patients under 65 years of age, independent of ELN risk group
Other Abstracts of Interest

ASH Abstract 793. Oligoblastic (<20%) Myeloid Neoplasms with KMT2A (MLL) Rearrangement Show Significant Overlap with Acute Myeloid Leukemia (AML) and Should be Regarded as AML
Sergej Konoplev et al.

ASH Abstract 692. Midostaurin Plus Intensive Chemotherapy for Younger and Older Patients with Acute Myeloid Leukemia and FLT3 Internal Tandem Duplications
Hartmut Döhner et al.

ASH Abstract 614. CD22ˡᵒʷ/Bcl-2ʰᶦᵍʰ Expression Identifies Poor Response to Inotuzumab in Relapsed/Refractory Acute Lymphoblastic Leukemia
Ernesto Diaz-Flores et al.