ASH 2017: Dasatinib Plus Standard Chemotherapy Demonstrates 3-Year Survival Benefit in Pediatric Patients With Philadelphia Chromosome–Positive ALL
At the 59th American Society of Hematology (ASH) Annual Meeting & Exposition, Hunger et al presented data from the phase II CA180-372 study in pediatric patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) treated with dasatinib (Sprycel) added to a chemotherapy regimen modeled on a Berlin-Frankfurt-Munster high-risk backbone (Abstract 98). The combination demonstrated an event-free survival rate (the study’s primary endpoint) of 65.5% (95% confidence interval [CI] = 57.7–73.7) and an overall survival rate of 91.5% (95% CI = 84.2–95.5) at 3 years. Dasatinib and chemotherapy were generally well tolerated in pediatric Philadelphia chromosome–positive ALL patients.
“Philadelphia chromosome–positive acute lymphoblastic leukemia remains a high-risk leukemia type,” said lead study author Stephen Hunger, MD, Chief of the Division of Oncology and Director of the Center for Childhood Cancer Research at Children’s Hospital of Philadelphia. “In this study, the addition of dasatinib to chemotherapy in pediatric patients with [Philadelphia chromosome–positive] ALL yielded similar event-free and overall survival rates to recent North American and European pediatric [Philadelphia chromosome–positive] ALL trials, with a lower percentage of patients undergoing hematopoietic stem cell transplantation in first remission, indicating the potential of dasatinib as a new treatment option for these patients.”
More on CA180-372
Patients treated in the study (n = 106), all aged younger than 18 years, received continuous daily dasatinib beginning at day 15 of induction chemotherapy. All treated patients achieved complete remission.
Patients who had evidence of minimal residual disease (MRD) ≥ 0.05% at the end of the first block of treatment (day 78) and those with MRD of 0.005% to 0.05% who remained MRD-positive at any detectable level after three additional high-risk chemotherapy blocks were eligible for hematopoietic stem cell transplantation (HSCT) in first remission. Among treated patients, 19 met these criteria and 15 (14.2%) received HSCT. The remaining 85.8% of patients received dasatinib plus chemotherapy for 2 years.
Patients received dasatinib at 60 mg/m2 as tablets or powder for oral suspension, once daily.
Two patients discontinued dasatinib due to toxicity—one due to allergy, and one due to prolonged thrombocytopenia. Primary toxicities of any causality included hematologic toxicity such as grade 3 or 4 febrile neutropenia (75.5%), sepsis (23.6%), and bacteremia (24.5%). Nonhematologic, noninfectious grade 3 or 4 adverse events attributed to dasatinib and reported in more than 10% of patients were limited to elevated levels of alanine aminotransferase (21.7%) and aspartate transaminase (10.4%).
Other grade 3 or 4 adverse events attributed to dasatinib were pleural effusion (3.8%), edema (2.8%), hemorrhage (5.7%), and cardiac failure (0.8%). No events of pulmonary hypertension or pulmonary arterial hypertension were reported. Seven deaths occurred during protocol therapy, with five patients receiving chemotherapy (three due to sepsis, one due to pneumonia, and one with unknown cause) and two being transplant-related.
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