학술논문
Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium
Document Type
Academic Journal
Author
Verma, Anupam; Chi, Yueh-Yun; Malvar, Jemily; Lamble, Adam; Chaudhury, Sonali; Agarwal, Archana; Li, Hong-Tao; Liang, Gangning; Leong, Roy; Brown, Patrick A.; Kaplan, Joel; Schafer, Eric S.; Slone, Tamra; Pauly, Melinda; Chang, Bill H.; Stieglitz, Elliot; Wayne, Alan S.; Hijiya, Nobuko; Bhojwani, Deepa
Source
Cancers. January 2024, Vol. 16 Issue 3
Subject
Language
English
ISSN
2072-6694
Abstract
Author(s): Anupam Verma (corresponding author) [1,2,*]; Yueh-Yun Chi [3]; Jemily Malvar [4]; Adam Lamble [5]; Sonali Chaudhury [6]; Archana Agarwal [7]; Hong-Tao Li [8]; Gangning Liang [8]; Roy Leong [4,‡]; [...]
The overall 5-year survival rate for children with acute myeloid leukemia (AML) has increased over time and is now in the range of 65% to 70%, but survival for patients who relapse continues to be poor. A phase I/II clinical trial was conducted by the pediatric consortium Therapeutic Advances in Childhood Leukemia & Lymphoma, with the aim to study immunotherapy along with azacitidine in children with relapsed AML. The combination was well tolerated in all the patients enrolled on the trial, with 33% having stable disease. In future studies, this combination in select pediatric patients with AML should be explored. Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3–4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.
The overall 5-year survival rate for children with acute myeloid leukemia (AML) has increased over time and is now in the range of 65% to 70%, but survival for patients who relapse continues to be poor. A phase I/II clinical trial was conducted by the pediatric consortium Therapeutic Advances in Childhood Leukemia & Lymphoma, with the aim to study immunotherapy along with azacitidine in children with relapsed AML. The combination was well tolerated in all the patients enrolled on the trial, with 33% having stable disease. In future studies, this combination in select pediatric patients with AML should be explored. Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3–4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.