Few treatment options, poor outcomes, especially in the elderly/unfit


  • Most common acute leukemia in adults; median age of diagnosis is 67 years of age (US). Age-adjusted incidence in the US is 12.2 per 100,000 (>65 yo) and 1.3 per 100,000 (<65 yo); incidence in the EU is 3.7 per 100,000
  • No targeted agents are currently approved for the treatment of AML. Chemotherapy is the current standard for care
    • Remission induction: Combination of cytarabine and an anthracycline (daunorubicin or idarubicin)
    • Consolidation: Post remission therapy involves high-dose cytarabine in younger patients; standard dose cytarabine/de-methylating agents in the elderly
    • Allogeneic bone marrow transplantation undertaken with curative intent is an option for post remission therapy in adults with AML
  • High unmet need in AML patients >65 years
    • Considered unfit for aggressive Tx, managed with low-intensity chemotherapy
    • Relapse rates/duration are poorer; primary refractory patients have a 5-year survival rate ≤10%
  • Maintenance is not yet established in AML
    • While ~60-70% patients achieve remission, a survival benefit for maintenance therapy has not yet been demonstrated












Biomarker-driven agents, therapies for the elderly/unfit likely to become available


  • AML lacks targeted drugs, but a number promising biomarker-based strategies have been identified:
  • FLT3-ITD mutations:
    • >30%, associated with poor outcomes
    • NVS plans to file for Midostaurin in H1 2016
    • >Quizartinib induces complete remissions with incomplete count recovery
    • >Crenolanib with ORR-47% in Phase II
  • Core-binding Factor (CBF) AML:
    • Characterized by rearrangements of t(8;21) and inv(16); despite favourable prognosis, relapses occur with adverse outcome related to cKIT and JAK2 Mu
    • Dasatinib + high-dose daunorubicin is being evaluated in CBF AML
  • IDH 1/2 mutations
    • 15-20% associated with poor prognosis
    • AG-221 with 41% ORR, 18% CR, DoR >6 months
    • AG-120 with 31% ORR, 15% CR
  • New therapies are also likely to become available for elderly/unfit patients:
    • Phase III, pre-reg study of Vosaroxin (Cytotoxic) demonstrated significant OS benefit in unfit AML
    • Lirilumab: encouraging Phase I data in maintenance
    • Volasertib: Breakthrough status, mOS: 8 vs. 5 months (LDAC)
    • CPX351: Induction RR- 47.7% – complex karyotype high-risk elderly; received Fast track status in elderly patients with secondary AML
    • WT-1 cancer vaccine exhibited promising Phase II results: mOS – ~53 months in adult AML patients
    • SGN CD33A: encouraging frontline Phase I data RR – 65%


Several opportunities in both frontline and relapsed AML, also in biomarker-driven segments

  • Given the high unmet need, opportunities exist in both frontline and R/R settings
    • Efficacious, tolerable bridge-to-transplant therapies
    • Chemo-free regimen with reduced toxicity/enhanced QoL, especially in the elderly
    • For additive efficacy, novel combinations with 7+3 (7 days of cytarabine + 3 days of anthracycline)
    • Need for efficacious and safe maintenance therapies
  • With an increase understanding of disease biology, several opportunities are emerging
    • Combinations/sequential therapies that attack multiple targets
      • AML marked with sequential emergence of resistant clones driven by multiple mutations/co-expression of markers
    • Personalized therapies
      • In emerging biomarker-driven segments , e.g., FLT3 Mu, IDH1/2 Mu
      • In CBF AML