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

Author:

Verma Anupam12ORCID,Chi Yueh-Yun3,Malvar Jemily4,Lamble Adam5,Chaudhury Sonali6,Agarwal Archana7,Li Hong-Tao8ORCID,Liang Gangning8,Leong Roy4,Brown Patrick A.9,Kaplan Joel10,Schafer Eric S.11,Slone Tamra12,Pauly Melinda13,Chang Bill H.14ORCID,Stieglitz Elliot15ORCID,Wayne Alan S.3,Hijiya Nobuko16ORCID,Bhojwani Deepa3

Affiliation:

1. Center for Cancer and Blood Disorders, Pediatric Hematology Oncology Branch, Children’s National Hospital, Washington, DC 20010, USA

2. Division of Pediatric Hematology Oncology, Primary Children’s Hospital, University of Utah, Salt Lake City, UT 84113, USA

3. Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA

4. Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA

5. Department of Pediatric Hematology Oncology, Seattle Children’s Hospital, Seattle, WA 98105, USA

6. Department of Pediatric Hematology Oncology, Ann and Robert Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA

7. Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT 84108, USA

8. Department of Urology, University of Southern California, Los Angeles, CA 90033, USA

9. Bristol Myers Squibb, Princeton, NJ 08543, USA

10. Department of Pediatric Hematology Oncology, Atrium Health Levine Children’s Hospital, Wake Forrest University, Charlotte, NC 28203, USA

11. Division of Pediatric Hematology/Oncology, Baylor College of Medicine, Texas Children’s Cancer and Hematology Center, Houston, TX 77030, USA

12. Department of Pediatric Hematology Oncology, UT Southwestern, Dallas, TX 75235, USA

13. Department of Pediatric Hematology Oncology, Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA

14. Division of Pediatric Hematology Oncology, Oregon Health and Science University, Portland, OR 97239, USA

15. Department of Pediatric Oncology, University of California, San Francisco Benioff Children’s Hospitals, San Francisco, CA 94158, USA

16. Division of Pediatric Hematology Oncology and Stem Cell Transplant, Columbia University Medical Center, New York, NY 10032, USA

Abstract

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.

Funder

Bristol Myers Squibb: Global Biopharmaceutical Company

Gateway for Cancer Research

Higgins Family Charitable Foundation

Publisher

MDPI AG

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