Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience
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 vene...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/7/1983 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adriana Trabal |
| collection | DOAJ |
| description | 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 <i>KMT2A</i> (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), <i>IDH1/2</i> (n = 2), monosomy 5 (n = 1), <i>NUP98</i> (n = 1) and <i>ASXL1</i> (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. |
| first_indexed | 2024-03-11T05:41:42Z |
| format | Article |
| id | doaj.art-35c5d62a24de43fd958bda52a78901b4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:41:42Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-35c5d62a24de43fd958bda52a78901b42023-11-17T16:24:27ZengMDPI AGCancers2072-66942023-03-01157198310.3390/cancers15071983Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center ExperienceAdriana Trabal0Amber Gibson1Jiasen He2David McCall3Michael Roth4Cesar Nuñez5Miriam Garcia6Meredith Buzbee7Laurie Toepfer8Aram Bidikian9Naval Daver10Tapan Kadia11Nicholas J. Short12Ghayas C. Issa13Farhad Ravandi14Courtney D. DiNardo15Guillermo Montalban Bravo16Sofia Garces17Andrea Marcogliese18Hana Paek19Zoann Dreyer20Julienne Brackett21Michele Redell22Joanna Yi23Guillermo Garcia-Manero24Marina Konopleva25Alexandra Stevens26Branko Cuglievan27Department of Pediatric Hematology/Oncology, Golisano Children’s Hospital, Fort Myers, FL 33908, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Pathology & Immunology, Texas Children’s Hospital, Houston, TX 77030, USADepartment of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USADepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Pediatrics, Section of Hematology/Oncology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAThe 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 <i>KMT2A</i> (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), monosomy 7 (n = 5), TP53 (n = 3), Inv(3) (n = 3), <i>IDH1/2</i> (n = 2), monosomy 5 (n = 1), <i>NUP98</i> (n = 1) and <i>ASXL1</i> (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.https://www.mdpi.com/2072-6694/15/7/1983acute myeloid leukemiapediatricchildrenvenetoclaxBcl-2 inhibitor |
| spellingShingle | 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 Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience Cancers acute myeloid leukemia pediatric children venetoclax Bcl-2 inhibitor |
| title | Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience |
| title_full | Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience |
| title_fullStr | Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience |
| title_full_unstemmed | Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience |
| title_short | Venetoclax for Acute Myeloid Leukemia in Pediatric Patients: A Texas Medical Center Experience |
| title_sort | venetoclax for acute myeloid leukemia in pediatric patients a texas medical center experience |
| topic | acute myeloid leukemia pediatric children venetoclax Bcl-2 inhibitor |
| url | https://www.mdpi.com/2072-6694/15/7/1983 |
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