General AML

ASH 2017 | Venetoclax with LDAC in treatment-naïve elderly patients with AML: a phase I/II study 

On Monday 11th December 2017, during the 59th American Society of Hematology (ASH) Annual Meeting, Atlanta, GA,  an oral abstract session focused on the use of novel therapies for elderly patients with Acute Myeloid Leukemia (AML). This oral session was moderated by Thomas Koehnke, from Stanford University and Amer M. Zeidan, from Yale Cancer Center.

Andrew Wei (chair of the AGP Rest of the World Steering Committee), from Alfred HospitalMonash University, Melbourne, Australia presented one of the key abstracts at this oral session.

Previous results obtained from a phase I study (NCT02287233), which evaluated the safety, pharmacokinetic profile, and efficacy of venetoclax (VEN) in combination with Low-Dose cytarabine (LDAC) in newly diagnosed AML patients, have shown that a VEN-LDAC combination is tolerable and durable in elderly AML patients. Additionally, the Recommended Phase 2 dose (RP2D) of VEN in combination with LDAC was found to be 600 mg. At the 22nd Congress of the European Hematology Association (EHA) Congress, Madrid, Spain, Andrew Wei, presented an updated follow up which showed that 600 mg VEN in combination with LDAC was tolerable and exhibited durable efficacy in elderly untreated AML patients.1

At this ASH oral session, Andrew Wei, presented the 1-year outcome and biomarker analysis from this phase I study. Overall, 61 AML patients (median age = 74 years) were treated with 600 mg VEN in combination with LDAC.2

Key data presented:
  • Safety
    • Treatment-emergent grade ≥ 3 Adverse Events (AEs) in patients (≥10%) were febrile neutropenia (36%), hypokalemia (16%), pneumonia (15%), AML progression (13%), hypertension (11%), hypophosphatemia (13%) and sepsis (10%)
    • 30-day early mortality rates: 3%
    • Death occurred as a result of disease progression (n = 1) and lung infection (n = 1)
  • CR/CRi rate in all patients was 62%
    • CR/CRi rate in patients (n = 7) with NPM1 mutation: 100%
    • CR/CRi rate in patients (n = 20) with TP53-aneuploidy: 50%
  • Median time to best response: 2.6 months (range, <1–14.4 months)
  • Median duration of CR/CRi: 13.2 months (range, 5.6–15.0 months)
  • 1-year OS: 46%
    • 1-year OS in patients (n = 7) with NPM1 mutation: not reached
    • 1-year OS in patients (n = 20) with TP53-aneuploidy: 6.5%
    • 1-year OS for patients who achieved CR and CRi were 100% and 49.2% respectively
  • Patients who achieved an objective response to VEN plus LDAC (n = 37) had longer survival than non-responders (n = 24)

Associate Prof. Andrew Wei concluded his talk by highlighting that 600 mg VEN in combination with LDAC has a low early mortality rate and demonstrated a clinically durable activity in elderly patients with newly diagnosed AML who are eligible for intensive chemotherapy. As a result of the findings of this study, a phase III randomized study (NCT03069352) of VEN co-administered with LDAC versus LDAC alone in treatment naïve patients with AML who are ineligible for intensive chemotherapy is currently underway.

  1. Wei A. et al. Updated safety and efficacy results of phase 1/2 study of venetoclax plus low-dose cytarabine in treatment-naïve acute myeloid leukemia patients aged ≥ 65 years and unfit for standard induction therapy. Abstract S473. 22nd Congress of the European Hematology Association; 2017 June 22–25; Madrid, Spain.
  2. Wei A. et al. Phase 1/2 Study of Venetoclax with Low-Dose Cytarabine in Treatment-Naive, Elderly Patients with Acute Myeloid Leukemia Unfit for Intensive Chemotherapy: 1-Year Outcomes. Oral Abstract #890: 59th ASH Annual Meeting and Exposition, Atlanta, GA.
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