Cancers (Mar 2023)

Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience

  • Adriana Trabal,
  • Amber Gibson,
  • Jiasen He,
  • David McCall,
  • Michael Roth,
  • Cesar Nuñez,
  • Miriam Garcia,
  • Meredith Buzbee,
  • Laurie Toepfer,
  • Aram Bidikian,
  • Naval Daver,
  • Tapan Kadia,
  • Nicholas J. Short,
  • Ghayas C. Issa,
  • Farhad Ravandi,
  • Courtney D. DiNardo,
  • Guillermo Montalban Bravo,
  • Sofia Garces,
  • Andrea Marcogliese,
  • Hana Paek,
  • Zoann Dreyer,
  • Julienne Brackett,
  • Michele Redell,
  • Joanna Yi,
  • Guillermo Garcia-Manero,
  • Marina Konopleva,
  • Alexandra Stevens,
  • Branko Cuglievan

DOI
https://doi.org/10.3390/cancers15071983
Journal volume & issue
Vol. 15, no. 7
p. 1983

Abstract

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The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions’ experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6–21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), IDH1/2 (n = 2), monosomy 5 (n = 1), NUP98 (n = 1) and ASXL1 (n = 1). The majority (86%) received venetoclax with a hypomethylating agent. Grade 3 or 4 adverse events included febrile neutropenia in 37% (n = 16), non-febrile neutropenia in 12% (n = 5), anemia in 14% (n = 6), and thrombocytopenia in 14% (n = 6). Of 40 patients evaluable for response, 10 patients (25%) achieved complete response (CR), 6 patients (15%) achieved CR with incomplete blood count recovery (CRi), and 2 patients (5%) had a partial response, (CR/CRi composite = 40%; ORR = 45%). Eleven (25%) patients received a hematopoietic stem cell transplant following venetoclax combination therapy, and six remain alive (median follow-up time 33.6 months). Median event-free survival and overall survival duration was 3.7 months and 8.7 months, respectively. Our findings suggest that in pediatric patients with AML, venetoclax is well-tolerated, with a safety profile similar to that in adults. More studies are needed to establish an optimal venetoclax-based regimen for the pediatric population.

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