PMID- 38339248
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240212
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 16
IP  - 3
DP  - 2024 Jan 24
TI  - 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.
LID - 10.3390/cancers16030496 [doi]
LID - 496
AB  - 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.
FAU - Verma, Anupam
AU  - Verma A
AUID- ORCID: 0000-0001-6555-7924
AD  - Center for Cancer and Blood Disorders, Pediatric Hematology Oncology Branch, 
      Children's National Hospital, Washington, DC 20010, USA.
AD  - Division of Pediatric Hematology Oncology, Primary Children's Hospital, 
      University of Utah, Salt Lake City, UT 84113, USA.
FAU - Chi, Yueh-Yun
AU  - Chi YY
AD  - 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.
FAU - Malvar, Jemily
AU  - Malvar J
AD  - Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's 
      Hospital Los Angeles, Los Angeles, CA 90027, USA.
FAU - Lamble, Adam
AU  - Lamble A
AD  - Department of Pediatric Hematology Oncology, Seattle Children's Hospital, 
      Seattle, WA 98105, USA.
FAU - Chaudhury, Sonali
AU  - Chaudhury S
AD  - Department of Pediatric Hematology Oncology, Ann and Robert Lurie Children's 
      Hospital of Chicago, Chicago, IL 60611, USA.
FAU - Agarwal, Archana
AU  - Agarwal A
AD  - Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake 
      City, UT 84108, USA.
FAU - Li, Hong-Tao
AU  - Li HT
AUID- ORCID: 0000-0001-6366-0741
AD  - Department of Urology, University of Southern California, Los Angeles, CA 90033, 
      USA.
FAU - Liang, Gangning
AU  - Liang G
AD  - Department of Urology, University of Southern California, Los Angeles, CA 90033, 
      USA.
FAU - Leong, Roy
AU  - Leong R
AD  - Division of Hematology-Oncology, Cancer and Blood Disease Institute, Children's 
      Hospital Los Angeles, Los Angeles, CA 90027, USA.
FAU - Brown, Patrick A
AU  - Brown PA
AD  - Bristol Myers Squibb, Princeton, NJ 08543, USA.
FAU - Kaplan, Joel
AU  - Kaplan J
AD  - Department of Pediatric Hematology Oncology, Atrium Health Levine Children's 
      Hospital, Wake Forrest University, Charlotte, NC 28203, USA.
FAU - Schafer, Eric S
AU  - Schafer ES
AD  - Division of Pediatric Hematology/Oncology, Baylor College of Medicine, Texas 
      Children's Cancer and Hematology Center, Houston, TX 77030, USA.
FAU - Slone, Tamra
AU  - Slone T
AD  - Department of Pediatric Hematology Oncology, UT Southwestern, Dallas, TX 75235, 
      USA.
FAU - Pauly, Melinda
AU  - Pauly M
AD  - Department of Pediatric Hematology Oncology, Children's Healthcare of Atlanta, 
      Atlanta, GA 30322, USA.
FAU - Chang, Bill H
AU  - Chang BH
AUID- ORCID: 0000-0003-3783-1820
AD  - Division of Pediatric Hematology Oncology, Oregon Health and Science University, 
      Portland, OR 97239, USA.
FAU - Stieglitz, Elliot
AU  - Stieglitz E
AUID- ORCID: 0000-0001-7032-4623
AD  - Department of Pediatric Oncology, University of California, San Francisco Benioff 
      Children's Hospitals, San Francisco, CA 94158, USA.
FAU - Wayne, Alan S
AU  - Wayne AS
AD  - 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.
FAU - Hijiya, Nobuko
AU  - Hijiya N
AUID- ORCID: 0000-0002-0199-054X
AD  - Division of Pediatric Hematology Oncology and Stem Cell Transplant, Columbia 
      University Medical Center, New York, NY 10032, USA.
FAU - Bhojwani, Deepa
AU  - Bhojwani D
AD  - 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.
LA  - eng
GR  - G-17-500/Gateway for Cancer Research/
GR  - CA209-9JY/Bristol Myers Squibb/
PT  - Journal Article
DEP - 20240124
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC10854518
OTO - NOTNLM
OT  - DNA methylation
OT  - acute myeloid leukemia
OT  - checkpoint inhibitor
OT  - dose-limiting toxicity
OT  - immunotherapy
COIS- G.L. is a consultant for PANGEA laboratory; A.S.W. receives research support from 
      Kite a Gilead company; S.C. is a consultant for Abbvie, Alexion, BluebirdBio; 
      N.H. receives research support from Novartis, Pfizer, is a consultant for 
      Novartis and Stemline Therapeutics and on DSMB for Incyte; P.A.B. is employed by 
      Bristol Myers-Squibb and holds stock in BMS; A.V., Y.-Y.C., J.M., D.B., E.S.S. 
      and B.H.C. do not have any conflicts of interest to report.
EDAT- 2024/02/10 10:47
MHDA- 2024/02/10 10:48
PMCR- 2024/01/24
CRDT- 2024/02/10 01:14
PHST- 2023/12/06 00:00 [received]
PHST- 2024/01/11 00:00 [revised]
PHST- 2024/01/19 00:00 [accepted]
PHST- 2024/02/10 10:48 [medline]
PHST- 2024/02/10 10:47 [pubmed]
PHST- 2024/02/10 01:14 [entrez]
PHST- 2024/01/24 00:00 [pmc-release]
AID - cancers16030496 [pii]
AID - cancers-16-00496 [pii]
AID - 10.3390/cancers16030496 [doi]
PST - epublish
SO  - Cancers (Basel). 2024 Jan 24;16(3):496. doi: 10.3390/cancers16030496.