Children's Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma
| Autor: | David T. Teachey, Meenakshi Devidas, Brent L. Wood, Zhiguo Chen, Robert J. Hayashi, Michelle L. Hermiston, Robert D. Annett, J. Hunter Archer, Barbara L. Asselin, Keith J. August, Steve Y. Cho, Kimberly P. Dunsmore, Brian T. Fisher, Jason L. Freedman, Paul J. Galardy, Paul Harker-Murray, Terzah M. Horton, Alok I. Jaju, Allison Lam, Yoav H. Messinger, Rodney R. Miles, Maki Okada, Samir I. Patel, Eric S. Schafer, Tal Schechter, Neelam Singh, Amii C. Steele, Maria Luisa Sulis, Sarah L. Vargas, Stuart S. Winter, Charlotte Wood, Patrick Zweidler-McKay, Catherine M. Bollard, Mignon L. Loh, Stephen P. Hunger, Elizabeth A. Raetz |
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| Rok vydání: | 2023 |
| Předmět: |
Cancer Research
Pediatric Research Initiative Lymphoma Childhood Leukemia Pediatric Cancer T-Lymphocytes Clinical Trials and Supportive Activities Clinical Sciences Oncology and Carcinogenesis Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Disease-Free Survival Bortezomib Young Adult Rare Diseases Clinical Research Antineoplastic Combined Chemotherapy Protocols Humans Oncology & Carcinogenesis Child Cancer Pediatric Evaluation of treatments and therapeutic interventions Infant Hematology ORIGINAL REPORTS Precursor Cell Lymphoblastic Leukemia-Lymphoma Orphan Drug Oncology 6.1 Pharmaceuticals |
| Zdroj: | J Clin Oncol Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol 40, iss 19 |
| ISSN: | 1527-7755 |
| Popis: | PURPOSE To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600). CONCLUSION Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse. |
| Databáze: | OpenAIRE |
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