Slayton WB, et al. - Experts evaluated the impact of dasatinib plus intensive chemotherapy on the survival of children and young adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. They noted a good tolerability of dasatinib with chemotherapy. It provided similar outcomes to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Limiting hematopoietic stem-cell transplantation (HSCT) to slow responders was supported in the findings. In rapid responders with IKZF1 deletions, a potential role for transplantation was suggested.

Methods

• Safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia, aged 1 to 30 years, was tested in children’s Oncology Group trial AALL0622 (Bristol Myers Squibb trial CA180-204).
• Researchers recommended the allogeneic hematopoietic stem-cell transplantation (HSCT) for patients at high risk based on slow response and for those with a matched family donor, regardless of response after at least 11 weeks of therapy.
• Chemotherapy plus dasatinib was received by patients for an additional 120 weeks if they were considered to be at standard risk based on rapid response.
• Cranial irradiation given to patients with overt CNS leukemia.

Results

• In total, 60 eligible patients were enrolled.
• Findings revealed that 5-year overall (OS) and event-free survival rates (± standard deviations [SD]) were 86% ± 5% and 60% ± 7% overall, 87% ± 5% and 61% ± 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% ± 13% and 67% ± 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively.
• Researchers reported 15% ± 6% as the 5-year cumulative incidence (± SD) of CNS relapse.
• Results demonstrated a similarity to the outcomes (± SDs) seen in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% ± 6% vs 86% ± 5% (P = .63) and 5-year disease-free survival of 68% ± 7% vs 60% ± 7% (P = 0.31) for AALL0031 vs AALL0622, respectively.
• Data suggested an association of IKZF1 deletions, present in 56% of tested patients, with significantly inferior OS and event-free survival overall and in standard-risk patients.