Dasatinib Receives FDA Approval for Pediatric Ph+ ALL

Article

Dasatinib (Sprycel) tablets has been approved by the FDA to be used in combination with chemotherapy for the treatment of pediatric patients &ge;1 year of age with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.<br /> &nbsp;

Dasatinib (Sprycel) tablets has been approved by the FDA to be used in combination with chemotherapy for the treatment of pediatric patients &ge;1 year of age with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

The FDA based the approval decision on findings from a single cohort of the phase II CA180-372 trial (NCT01460160). Results showed a 3-year event-free survival (EFS) binary rate of 64.1% (95% CI, 52.4%-74.7%) in 78 pediatric patients with newly diagnosed B-cell precursor Ph+ ALL.

&ldquo;As treatments have advanced in recent years, we&rsquo;ve seen improvements in outcomes for pediatric patients with Ph+ ALL overall, but there remains a need for additional options,&rdquo; said Stephen Hunger, MD, lead study author, chief of the division of oncology and director of the Center for Childhood Cancer Research at Children&rsquo;s Hospital of Philadelphia, in a press release. &ldquo;The phase II CA180-372 trial was particularly informative because it was designed to limit the use of cranial irradiation and stem cell transplant. In the study, Sprycel plus chemotherapy demonstrated a three-year event-free survival benefit. These results show that Sprycel is an effective medication for physicians to consider for children and adolescents with Ph+ ALL.&rdquo;

The phase II study included 106 patients aged <18 years old were treated with continuous daily dasatinib starting at day 15 of induction chemotherapy. The 78 patients evaluated for efficacy in cohort 1 received dasatinib at 60 mg/m2daily for up to 2 years in combination with a backbone chemotherapy regimen of the AIEOP-BFM ALL 2000 multi-agent chemotherapy protocol. Additionally, patients were assigned to receive stem cell transplant based on minimal residual disease if they were considered high-risk.

A complete remission was achieved by all treated patients. At day 78 (end of first block of treatment), patients with minimal residual disease (MRD) &ge;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.

Among the 81 patients evaluated for safety, grade 5 adverse events (AEs) occurred in 3 patients (4%), and 8 patients (10%) experienced AEs leading to treatment discontinuation, including fungal sepsis, hepatotoxicity of graft-versus-host disease, thrombocytopenia, CMV infection, pneumonia, nausea, enteritis and drug hypersensitivity. The most common serious AEs occurring in &ge;10% of patients were pyrexia, febrile neutropenia, mucositis, diarrhea, sepsis, hypotension, infections, hypersensitivity, vomiting, renal insufficiency, abdominal pain and musculoskeletal pain.

&ldquo;We recognize the urgency around developing and delivering therapies for children and young adults living with cancer, and today&rsquo;s approval is an important example of our commitment to pediatric oncology,&rdquo; said Jeffrey Jackson, PhD, development lead, hematology, Bristol-Myers Squibb, the manufacturer of dasatinib, in a press release. &ldquo;Building on our previous indication for children with Ph+ chronic myeloid leukemia in chronic phase, we&rsquo;re pleased to bring Sprycel tablets to a second type of pediatric leukemia. This approval will give physicians another treatment option to offer appropriate pediatric patients with Ph+ ALL.&rdquo;

The FDA initially approved dasatinib in November 2017 for the treatment of pediatric patients with Ph+ chronic myeloid leukemia in chronic phase.

ALL represents 20% of all cancers diagnosed in patients aged less than 20 years, or more than 3000 new cases annually. Three percent of children who have ALL have Ph+ disease.

Reference:

Bristol-Myers Squibb&rsquo;s Sprycel&reg; (dasatinib) Tablets Now Approved in Combination with Chemotherapy in Certain Pediatric Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Bristol-Myers Squibb. Published January 2, 2019. https://bit.ly/2F230c5?rel=0" . Accessed January 2, 2019.

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