Dasatinib Is Safe and Effective in Philadelphia Chromosome-positive Pediatric ALL
Researchers assessed the efficacy of dasatinib — a TKI that is significantly more potent than imatinib and is active even in the setting of imatinib resistance — in this patient population.
|The following article features coverage from the American Society of Hematology (ASH) 2017 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
Adding dasatinib to the EsPhALL regimen was safe and effective for pediatric patients with Philadelphia chromosome–positive (Ph+) acute lymphocytic leukemia (ALL), according to an oral presentation at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.1
Previous studies demonstrated that adding the tyrosine kinase inhibitor (TKI) imatinib to various chemotherapy regimens improved event-free survival (EFS) and overall survival (OS) in pediatric Ph+ ALL.
For this phase 2 study, investigators administered dasatinib, a TKI more potent than imatinib, to 106 pediatric patients on day 15 of induction chemotherapy in addition to the EsPhALL chemotherapy backbone regimen, and evaluated patient minimal residual disease (MRD).
Patients with MRD 0.05% and greater and those with MRD 0.005% to 0.05% at the end of day 78 (block Ib) who were MRD-positive after 3 additional cycles of high-risk chemotherapy underwent hematopoietic stem cell transplant (HSCT) during first remission (CR1). Dasatinib treatment after HSCT was optional.
At time of analysis, all patients completed therapy and 75% of patients had a follow-up period of longer than 3 years. Fifteen patients underwent HSCT in CR1, and the remaining 91 patients received EsPhALL plus dasatinib without HSCT. All 104 patients with Ph+ ALL (2 of the original patients were incorrectly diagnosed) had a complete response (CR).
The 3-year EFS and OS rates were 66.0% (95% CI, 54.8-75.0) and 92.3% (95% CI, 85.2-96.1), respectively.
As of the study lock date, 33 events occurred, including 5 deaths attributed to proven or suspected infection among the 91 patients treated with chemotherapy and dasatinib, 2 deaths from post-HSCT infection, and 26 cases of relapse (22/86 chemotherapy patients, 4/12 HSCT patients).
Two patients discontinued because of toxicity; 1 patient had a hypersensitivity reaction and the other experienced prolonged myelosuppression post-HSCT. The most frequently reported grade 3 or worse adverse events included febrile neutropenia in 75.5% of patients, sepsis in 18.9%, and bacteremia in 13.2%.
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- Hunger SP, Saha V, Devidas M, et al. An international collaborative phase 2 trial of dasatinib and chemotherapy in pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Oral presentation at: American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.