TY - JOUR
T1 - Venetoclax for Acute Myeloid Leukemia in Pediatric Patients
T2 - A Texas Medical Center Experience
AU - Trabal, Adriana
AU - Gibson, Amber
AU - He, Jiasen
AU - McCall, David
AU - Roth, Michael
AU - Nuñez, Cesar
AU - Garcia, Miriam
AU - Buzbee, Meredith
AU - Toepfer, Laurie
AU - Bidikian, Aram
AU - Daver, Naval
AU - Kadia, Tapan
AU - Short, Nicholas J.
AU - Issa, Ghayas C.
AU - Ravandi, Farhad
AU - DiNardo, Courtney D.
AU - Montalban Bravo, Guillermo
AU - Garces, Sofia
AU - Marcogliese, Andrea
AU - Paek, Hana
AU - Dreyer, Zoann
AU - Brackett, Julienne
AU - Redell, Michele
AU - Yi, Joanna
AU - Garcia-Manero, Guillermo
AU - Konopleva, Marina
AU - Stevens, Alexandra
AU - Cuglievan, Branko
N1 - Funding Information:
This research was funded by National Institutes of Health (P30 CA016672).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - Bcl-2 inhibitor
KW - acute myeloid leukemia
KW - children
KW - pediatric
KW - venetoclax
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U2 - 10.3390/cancers15071983
DO - 10.3390/cancers15071983
M3 - Article
C2 - 37046645
AN - SCOPUS:85152916077
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 7
M1 - 1983
ER -