Long-Term Outcomes With Dasatinib Plus Intensive Chemotherapy in Pediatric/Young Adult Ph-Positive ALL
In an analysis of the Children’s Oncology Group (COG) AALL0622 trial reported in the Journal of Clinical Oncology, Slayton et al found that adding dasatinib (Sprycel) to intensive chemotherapy produced good long-term outcomes in pediatric/young adult patients with newly diagnosed Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). In the earlier COG AALL0031 trial, the addition of imatinib (Gleevec) to the same intensive chemotherapy improved survival in this setting, with all patients receiving cranial irradiation. Dasatinib is active against imatinib-resistant clones and exhibits better CNS penetration.
Study Details
The study involved 60 eligible patients with a mean age of 10 years at diagnosis enrolled from 47 institutions between July 2008 and February 2012. Patients initiated dasatinib treatment at induction day 15 (compared with initiation of imatinib on day 1 of consolidation in the AALL0031 trial). Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended 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. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia (n = 11) received cranial irradiation.
Long-Term Outcomes
At 5 years, overall survival was 86% and event-free survival was 60% among all patients, 87% and 61% among 48 standard-risk patients (HSCT in 19%), and 89% and 67% in 9 high-risk patients (HSCT in 89%). The cumulative incidence of CNS relapse at 5 years was 15%. Outcomes were similar to those with imatinib plus chemotherapy in COG AALL0031: 5-year overall survival of 81% vs 86% (P = .63 vs AALL0622) and 5-year disease-free survival of 68% vs 60% (P = 0.31 vs ALL0622).
IKZF1 deletions were present in 25 (56%) of 44 tested patients. Presence vs absence of the deletions was associated with poorer 5-year overall survival (80% vs 100%, P = .04) and event-free survival (52% vs 82%, P = .04).
The investigators concluded,“Dasatinib… [plus chemotherapy] provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.”
William B. Slayton, MD, of the Department of Pediatrics, University of Florida at Gainesville, is the corresponding author for the Journal of Clinical Oncology article.
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