ASH 2019 – Pediatric acute myeloid leukemia: venetoclax plus high-dose cytarabine safe, effective in phase 2


  • W. Todd Penberthy, Ph.D.
  • Univadis
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Takeaway

  • Venetoclax (60 mg/m2 daily [max 600 mg] for 28 days) combined with high-dose cytarabine (100 mg/m2) with or without idarubicin (12 mg/m2) was well tolerated and effective in children and young adults with relapsed or refractory acute myeloid leukemia (AML).
  • The most common toxicities were infections, including culture-negative febrile neutropenia, sepsis, and colitis. 

 Why this matters

  • The BCL-2 inhibitor venetoclax has shown efficacy in adult patients with AML.

 Study design

  • Study evaluated venetoclax in combination with high-dose cytarabine with or without idarubicin in children and young adults with relapsed or refractory AML (n=36; age, 2-22 years).
  • Venetoclax was given daily for 28 days and chemotherapy was started on day 8, or earlier in cases of disease progression.  
  • Bone marrow was evaluated between days 29-50 of therapy. 
  • Funding: Abbvie.

Key results

  • The recommended phase 2 dose of venetoclax was 360 mg/m2 daily (max 600 mg).
  • Venetoclax levels were consistent across weights and ages and similar to those seen in adults. 
  • 22 patients received venetoclax with high-dose cytarabine±idarubicin.
  • 64% of patients achieved a complete response (CR) or complete response with incomplete count recovery (CRi).
  • Partial response/CR/CRi was observed in 87% of patients with >80% reduction in peripheral blasts vs 53% with
  • Patients experienced a mean of 2.4 nonhematologic grade ≥3 toxicities; most common were infections, including culture-negative febrile neutropenia (66%), sepsis (5.2%), and colitis.
  • Patient-reported QoL was unchanged at the completion of cycle 1. 

Limitations

  • No comparator.