DASATINIB IN CHILDREN AND ADOLESCENTS WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML-CP) FROM A PHASE 2 TRIAL
Author(s): ,
C. Michel Zwaan
Affiliations:
Erasmus MC-Sophia Children's Hospital,Rotterdam,Netherlands
,
Pamela Kearns
Affiliations:
University of Birmingham,Birmingham, West Midlands,United Kingdom
,
Maria Lucia de Martino Lee
Affiliations:
Support Group for Children and Adolescents with Cancer,São Paulo,Brazil
,
Carmino Antonio De Souza
Affiliations:
University of Campinas,São Paulo,Brazil
,
Yves Bertrand
Affiliations:
L'Institut d'Hématologie et d'Oncologie Pédiatrique,Lyon,France
,
Nobuko Hijiya
Affiliations:
Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine,Chicago,United States
,
Linda Stork
Affiliations:
Oregon Health & Science University,Portland,United States
,
Nack-Gyun Chung
Affiliations:
The Catholic University of Korea, Seoul St. Mary's Hospital,Seoul,Korea, Republic Of
,
Rocio Cardenas Cardos
Affiliations:
Instituto Nacional De Pediatría,Mexico City,Mexico
,
Tapan Saikia
Affiliations:
Prince Aly Khan Hospital,Mumbai,India
,
Franca Fagioli
Affiliations:
Regina Margherita Hospital,Turin,Italy
,
Jong Jin Seo
Affiliations:
University of Ulsan College of Medicine, Asan Medical Center,Seoul,Korea, Republic Of
,
Judith Landman-Parker
Affiliations:
Hôpital Enfants Armand-Trousseau,Paris,France
,
Donna Lancaster
Affiliations:
Royal Marsden Hospital,Sutton, Surrey,United Kingdom
,
Andrew E. Place
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Karen R. Rabin
Affiliations:
Texas Children's Cancer Center, Baylor College of Medicine,Houston,United States
,
Mariana Sacchi
Affiliations:
Bristol-Myers Squibb,Princeton,United States
,
Rene Swanink
Affiliations:
Bristol-Myers Squibb,Princeton,United States
Lia Gore
Affiliations:
University of Colorado School of Medicine/Children's Hospital Colorado,Aurora,United States
EHA Library. Zwaan C. Jun 24, 2017; 181709; S422
Christian Michel Zwaan
Christian Michel Zwaan
Contributions
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Abstract

Abstract: S422

Type: Oral Presentation

Presentation during EHA22: On Saturday, June 24, 2017 from 11:30 - 11:45

Location: Hall D

Background
As safe and effective frontline treatment options for children and adolescents with CML are limited, and no approved therapies exist for patients (pts) resistant/intolerant to imatinib (IM), additional treatment options and alternative formulations are greatly needed for this younger population. Dasatinib (DAS) has proven efficacy in adults with newly diagnosed CML-CP, as well as those resistant/intolerant to IM (Cortes JCO 2016, Shah AJH 2016). Results of a phase 1 study confirmed its dosing and safety in pediatric pts (Zwaan JCO 2013); however, a larger prospective study is necessary to further support the use of DAS in pediatric pts with newly diagnosed or IM-resistant/intolerant CML-CP.

Aims
To determine whether DAS is safe and effective in pediatric pts with CML-CP newly diagnosed or resistant/intolerant to IM enrolled in a phase 2, open-label, nonrandomized prospective clinical trial (CA180-226/NCT00777036).

Methods
Pts aged <18 years were recruited into 3 separate cohorts: (1) IM-resistant/intolerant CML-CP treated with DAS tablets 60 mg/m2 QD, (2) IM-resistant/intolerant CML-AP/BP or Ph+ ALL (enrollment closed early due to poor response), and (3) newly diagnosed CML-CP treated with DAS tablets 60 mg/m2 or DAS 72 mg/m2 powder for oral suspension (PFOS) QD for ≥1 year. PFOS dose was increased by 20% to match the exposure of the tablet in order to maintain a desired efficacy based on the findings from a bioequivalence study in adults. Primary objectives were major cytogenetic response (MCyR) for CML-CP resistant/intolerant to IM and complete cytogenetic response (CCyR) for newly diagnosed CML-CP (MCyR >30% and CCyR >55% considered of clinical interest). Study cohorts were not designed to be comparative.

Results
From 145 pts enrolled, 130 were treated; 54% were aged ≥12–<18 years. Within the IM resistant/intolerant group, 25 were resistant, 2 were intolerant, and 2 were undetermined. For pts with CML-CP (n=113), 48% of pts with IM-resistant/intolerant CML-CP and 73% with newly diagnosed CML-CP remained on treatment at the time of this analysis (table). Cumulative rate of MCyR >30% was reached as early as 3 months for IM-resistant/intolerant CML-CP, and a cumulative rate of CCyR >55% was reached as early as 6 months for newly diagnosed CML-CP (table). Estimated progression-free survival (PFS) by 48 months was 78% for IM-resistant/intolerant CML-CP and 93% for newly diagnosed CML-CP (table). Reasons for progression were loss of MCyR (n=3 IM-resistant/intolerant; n=4 newly diagnosed), loss of complete hematologic response (n=2 each), and development of CML-BP (n=2 IM-resistant/intolerant; n=1 newly diagnosed). One death was reported in the IM-resistant/intolerant CML-CP cohort 1 year after stopping DAS (gastrointestinal bleeding). Adverse events (AEs) were consistent with reports in DAS-treated adults, except no DAS-related pleural/pericardial effusion, pulmonary edema/hypertension, or pulmonary arterial hypertension were reported here. Hypersensitivity in a newly diagnosed pt was the only DAS-related AE that led to discontinuation.

Conclusion
Results from the largest prospective and registrational trial of pediatric pts with CML-CP demonstrate that DAS is a safe and effective treatment for pediatric CML-CP. Target responses to first- or second-line that DAS were met as early as 3 and 6 months, respectively, and deep responses were observed. Efficacy and safety of DAS in pediatric pts were similar to those observed in adults; however, unlike in adults, no cases of pleural/pericardial effusion were reported.

Session topic: 8. Chronic myeloid leukemia - Clinical

Keyword(s): Tyrosine kinase inhibitor, Pediatric, Chronic myeloid leukemia

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