The FDA has accepted a supplemental biologics license application (sBLA) for dasatinib (Sprycel) for use in combination with chemotherapy for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL).1UPDATE 1/2/2019: FDA Approves Dasatinib for Pediatric Ph+ ALL
The sBLA is supported by data from the phase II CA180-372 (NCT01460160) trial, in which pediatric patients with newly diagnosed Ph+ ALL received dasatinib added to a chemotherapy regimen modelled on a Berlin-Frankfurt-Munster high-risk backbone, according to Bristol-Myers Squibb, the manufacturer of the tyrosine kinase inhibitor. In results presented at the 2017 ASH Annual Meeting, the 3-year event-free survival rate for the dasatinib combination was 65.5% (95% CI, 57.7 -73.7), and the 3-year overall survival (OS) rate was 91.5% (95% CI, 84.2-95.5).2
The FDA is scheduled to make its decision on the sBLA by December 29, 2018.
“Sprycel was first established as an important treatment option for appropriate pediatric patients last year, when it was approved for the treatment of children with Ph+ chronic myeloid leukemia,” Jeffrey Jackson, PhD, development lead, hematology, Bristol-Myers Squibb, said in a statement.
“This latest milestone in Ph+ ALL reinforces our commitment to researching the potential of Sprycel in different types of pediatric leukemia and to providing this vulnerable population with access to potential new therapies,” added Jackson.
In the phase II study, 106 patients aged <18 years old were treated with continuous daily dasatinib starting at day 15 of induction chemotherapy. A complete remission was achieved by all treated patients. At day 78 (end of first block of treatment), patients with minimal residual disease (MRD) ≥0.05% were eligible for hematopoietic stem cell transplantation (HSCT) in first remission, as were patients with MRD 0.005% to 0.05% who were still MRD-positive following an additional 3 high-risk chemotherapy blocks. Nineteen of the 106 treated patients met these criteria, with 14.2% (n = 15), being treated with HSCT. The other 91 patients received 2 years of treatment with dasatinib combined with chemotherapy.
Grade 3/4 adverse events (AEs) included febrile neutropenia (75.5%), sepsis (23.6%), bacteremia (24.5%), elevated ALT (21.7%), elevated AST (10.4%), pleural effusion (3.8%), edema (2.8%), hemorrhage (5.7%), and cardiac failure (0.8%).
AE-related discontinuations occurred in 2 patients, 1 linked to allergy and 1 due to thrombocytopenia. During protocol therapy, there were 7 patient deaths. Two deaths were transplant-related and 5 were in patients receiving chemotherapy (sepsis, 3; pneumonia, 1; unknown cause, 1).
“Philadelphia chromosome–positive acute lymphoblastic leukemia remains a high-risk leukemia type,” lead study investigator Stephen Hunger, MD, chief of the Division of Oncology and Director of the Center for Childhood Cancer Research at Children’s Hospital of Philadelphia, said in a statement at the time the data were presented at the 2017 ASH Annual Meeting.
“In this study, the addition of dasatinib to chemotherapy in pediatric patients with Ph+ ALL yielded similar event-free and overall survival rates to recent North American and European pediatric Ph+ 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,” added Hunger.
In November 2017, the FDA approved dasatinib for the treatment of pediatric patients with Ph+ chronic myeloid leukemia in chronic phase.
- U.S. Food and Drug Administration Accepts Bristol-Myers Squibb’s Application for Sprycel (dasatinib) in Pediatric Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Posted August 30, 2018. Accessed August 30, 2018. https://bit.ly/2LLh1Ko?rel=0" .
- Sprycel (dasatinib) Added to Standard Chemotherapy Demonstrates Three-Year Survival Benefit in Pediatric Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Posted December 9, 2017. Accessed August 30, 2018. https://bit.ly/2MEcNta?rel=0" .