FDA Approves Sprycel for Pediatric ALL

The Food and Drug Administration (FDA) approved Sprycel (dasatinib) plus chemotherapy for the treatment of pediatric patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), according to Bristol-Myers Squibb, the manufacturer of the drug.

The approval was based off CA180-372, a phase 2 trial where pediatric patients with newly diagnosed Ph+ ALL received Sprycel plus a chemotherapy regimen that was modeled on a Berlin-Frankfurt-Munster high-risk backbone.

In the phase 2 study, 106 patients aged younger than 18 years old were treated with continuous daily Sprycel starting at day 15 of induction chemotherapy. The 78 patients evaluated for efficacy in cohort one received Sprycel at 60 mg/m² daily for up to two 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.

Results showed that a complete remission was achieved by all treated patients. At day 78 (end of first block of treatment), patients with minimal residual disease (MRD) of at least 0.05 percent were eligible for hematopoietic stem cell transplantation (HSCT) in first remission, as were patients with MRD 0.005 percent to 0.05 percent who were still MRD-positive following an additional three high-risk chemotherapy blocks. Nineteen of the 106 treated patients met these criteria, with 14.2 percent (15 patients), being treated with HSCT. The other 91 patients received two years of treatment with Sprycel combined with chemotherapy.

Of the 81 patients evaluated for safety, grade 5 adverse events (AEs) occurred in three patients (4 percent), and eight patients (10 percent) 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 side effects occurring in 10 percent or more of patients were pyrexia, febrile neutropenia, mucositis, diarrhea, sepsis, hypotension, infections, hypersensitivity, vomiting, renal insufficiency, abdominal pain and musculoskeletal pain.

“In pediatric cancer patients, Philadelphia chromosome-positive acute lymphoblastic leukemia is a rare, high-risk subtype and additional treatment options are sorely needed. Adults with chronic myeloid leukemia who received dasatinib achieved molecular remission earlier than those treated with imatinib. Although a clinical randomized study must still be performed, dasatinib is expected to have an even stronger response against pediatric Philadelphia-chromosome-positive ALL, and potentially benefit those patients” said Hiroto Inaba, M.D., Ph.D., a member of the Oncology Department at St. Jude Children’s Research Hospital in an interview with CURE.

Side effects to be cautious of when taking Sprycel include: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome and embryo-fetal toxicity.

While this is an exciting advance in the field, Inaba mentioned that there is still more work that needs to be done.

“Additional research is needed to assure the utility of dasatinib for pediatric patients with Philadelphia chromosome-positive ALL,” Inaba said.