TY - JOUR
T1 - Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase
T2 - Results from a phase II trial
AU - Gore, Lia
AU - Kearns, Pamela R.
AU - de Martino Lee, Maria Lucia
AU - De Souza, Carmino Antonio
AU - Bertrand, Yves
AU - Hijiya, Nobuko
AU - Stork, Linda C.
AU - Chung, Nack Gyun
AU - Cardos, Rocio Cardenas
AU - Saikia, Tapan
AU - Fagioli, Franca
AU - Seo, Jong Jin
AU - Judith, Landman Parker
AU - Lancaster, Donna
AU - Place, Andrew E.
AU - Rabin, Karen R.
AU - Sacchi, Mariana
AU - Swanink, Rene
AU - Zwaan, C. Michel
N1 - Publisher Copyright:
© 2018 by American Society of Clinical Oncology.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients, 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response . 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) . 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response . 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR . 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.
AB - Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients, 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response . 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) . 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response . 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR . 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.
UR - https://www.scopus.com/pages/publications/85046036154
U2 - 10.1200/JCO.2017.75.9597
DO - 10.1200/JCO.2017.75.9597
M3 - Article
C2 - 29498925
AN - SCOPUS:85046036154
SN - 0732-183X
VL - 36
SP - 1330
EP - 1338
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 13
ER -