Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience
by
, , , , , , , , ,
Adriana Trabal
1,†,
Amber Gibson
2,†,
Jiasen He
2,
David McCall
2,
Michael Roth
2,
Cesar Nuñez
2,
Miriam Garcia
2,
Meredith Buzbee
2,
Laurie Toepfer
2,
Aram Bidikian
3,
Naval Daver
3, 
Tapan Kadia
3,
Nicholas J. Short
3, 
Ghayas C. Issa
3,
Farhad Ravandi
3, 
Courtney D. DiNardo
3,
Guillermo Montalban Bravo
3,
Sofia Garces
4,
Andrea Marcogliese
5,
Hana Paek
6,
Zoann Dreyer
6,
Julienne Brackett
6,
Michele Redell
6,
Joanna Yi
6,
Guillermo Garcia-Manero
3,
Marina Konopleva
7,
Alexandra Stevens
6,‡ and
Branko Cuglievan
2,*,‡add
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1
Department of Pediatric Hematology/Oncology, Golisano Children’s Hospital, Fort Myers, FL 33908, USA
2
Department of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
3
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
4
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
5
Department of Pathology & Immunology, Texas Children’s Hospital, Houston, TX 77030, USA
6
Department of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USA
7
Department of Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work as co-first authors.
‡
These authors contributed equally to this work as co-senior authors.
Cancers 2023, 15(7), 1983; https://doi.org/10.3390/cancers15071983
Submission received: 7 February 2023
/
Revised: 7 March 2023
/
Accepted: 21 March 2023
/
Published: 26 March 2023
(This article belongs to the Special Issue Advances in Pediatric Acute Myeloid Leukemia)
Simple Summary
Pediatric patients with relapsed or refractory acute myeloid leukemia (AML) have poor survival with current therapy. Venetoclax is a small molecule inhibitor that has shown promise in both adult and pediatric leukemias. Here we describe the joint experience of the Texas Medical Center (The University of Texas MD Anderson Cancer Center and Baylor College of Medicine/Texas Children’s Hospital) use of venetoclax in combination with various therapies for the treatment of pediatric relapsed AML. We report the safety and efficacy of this regimen in this population.
Abstract
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.
Keywords:
acute myeloid leukemia; pediatric; children; venetoclax; Bcl-2 inhibitor
