TY - JOUR
T1 - A phase 2 study of nilotinib in pediatric patients with CML
T2 - Long-term update on growth retardation and safety
AU - Hijiya, Nobuko
AU - Maschan, Alexey
AU - Rizzari, Carmelo
AU - Shimada, Hiroyuki
AU - Dufour, Carlo
AU - Goto, Hiroaki
AU - Kang, Hyoung Jin
AU - Guinipero, Terri
AU - Karakas, Zeynep
AU - Bautista, Francisco
AU - Ducassou, Stephane
AU - Yoo, Keon Hee
AU - Zwaan, Christian Michel
AU - Millot, Frederic
AU - Patterson, Briana
AU - Samis, Jill
AU - Aimone, Paola
AU - Allepuz, Alex
AU - Titorenko, Ksenia
AU - Sosothikul, Darintr
AU - Bautista Sirvent, Paco
N1 - Publisher Copyright:
© 2021 by The American Society of Hematology.
PY - 2021/7/27
Y1 - 2021/7/27
N2 - The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. This update assessed growth and safety profiles in patients who had completed ≥48, 28-day treatment cycles of nilotinib 230 mg/m2 twice daily, or previously discontinued the study. Height was assessed regularly and reported using standard deviation scores (SDSs) based on World Health Organization growth charts. All data were summarized descriptively (cutoff, 6 March 2019). Overall, 33 patients in the R/I cohort and 25 patients in the ND cohort received nilotinib. Each cohort showed a negative slope in height SDS over the course of the study, indicating attenuated growth rates during nilotinib treatment: overall median change from baseline in height SDS after 48 cycles was 20.54 SDS (range, 2 1.6 to 0.4) and 20.91 SDS (21.4 to 20.1) in R/I and ND cohorts, respectively. Patients in the R/I cohort were shorter at baseline than those in the ND cohort, and remained so throughout the study. The most common all-cause adverse events were increased blood bilirubin (53.4%), headache (46.6%), pyrexia (37.9%), and increased alanine transferase (36.2%). Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765.
AB - The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. This update assessed growth and safety profiles in patients who had completed ≥48, 28-day treatment cycles of nilotinib 230 mg/m2 twice daily, or previously discontinued the study. Height was assessed regularly and reported using standard deviation scores (SDSs) based on World Health Organization growth charts. All data were summarized descriptively (cutoff, 6 March 2019). Overall, 33 patients in the R/I cohort and 25 patients in the ND cohort received nilotinib. Each cohort showed a negative slope in height SDS over the course of the study, indicating attenuated growth rates during nilotinib treatment: overall median change from baseline in height SDS after 48 cycles was 20.54 SDS (range, 2 1.6 to 0.4) and 20.91 SDS (21.4 to 20.1) in R/I and ND cohorts, respectively. Patients in the R/I cohort were shorter at baseline than those in the ND cohort, and remained so throughout the study. The most common all-cause adverse events were increased blood bilirubin (53.4%), headache (46.6%), pyrexia (37.9%), and increased alanine transferase (36.2%). Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765.
UR - http://www.scopus.com/inward/record.url?scp=85111558326&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2020003759
DO - 10.1182/bloodadvances.2020003759
M3 - Article
AN - SCOPUS:85111558326
SN - 2473-9529
VL - 5
SP - 2925
EP - 2934
JO - Blood Advances
JF - Blood Advances
IS - 14
ER -