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 - Funding Information:
We thank the patients who participated in this study and the clinical study teams. We thank Dr. Yousif Matloub for his work developing this study and Eric Bleickardt for clinical development contributions to this study. Medical writing and editorial support were provided by Samantha L. Dwyer and Andrea Lockett of StemScientific, an Ashfield Company (Lyndhurst, NJ), and were funded by Bristol-Myers Squibb.
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.
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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 -