Two genetic subtypes of childhood B-cell acute lymphoblastic leukemia (B-ALL) have long been associated with inferior treatment outcomes: Philadelphia chromosome-positive (Ph+) and ABL-class Philadelphia chromosome-like (Ph-like) B-ALL. In recent years the upfront addition of targeted tyrosine kinase inhibitors (TKIs) to chemotherapy has made significant inroads against these subtypes by suppressing the abnormal tyrosine kinase signaling driven by their specific mutations. However, there remains an urgent need for improved treatments, as even with the addition of TKIs, the five-year overall survival for Ph+ and Ph-like B-ALL remains approximately 80%.
A phase 3 clinical trial run by the Children’s Oncology Group and now recruiting at Roswell Park Comprehensive Cancer Center aims to determine whether survival can be improved in pediatric, adolescent and young adult patients by adding the T-cell immunotherapy blinatumomab (brand name Blincyto) to a regimen that combines chemotherapy with one of two different TKIs. Lisa Niswander, MD, PhD, Assistant Professor of Oncology in the Pediatric Oncology Department, is site Principal Investigator of the study (NCT06124157), which is sponsored by the National Cancer Institute.
Blinatumomab, a bispecific T-cell engager (BiTE) antibody, enables a patient’s T cells to zero in on and bind to the CD19 protein found on the surface of B-ALL cells, harnessing the immune system to specifically target the killing of the leukemia cells. Imatinib and dasatinib, both TKIs, work by blocking the action of abnormal proteins that promote the growth and division of cancer cells.
Among other eligibility requirements, patients who enroll in the study must be younger than 25 years of age and newly diagnosed with either Ph+ B-ALL or Ph-like B-ALL. They will be assigned to one of two treatment regimens based on their molecular B-ALL subtype:
- Those with Ph+ B-ALL will receive a modified Berlin-Frankfurt-Münster chemotherapy regimen along with three cycles of blinatumomab — without traditional consolidation chemotherapy — and continuous dasatinib.
- Those with Ph-like B-ALL will receive a modified Berlin-Frankfurt-Münster chemotherapy — without traditional consolidation chemotherapy — plus either continuous imatinib for those with PDGFRB gene fusions or dasatinib for those without.
Investigators will focus primarily on the safety and toxicity profile of these regimens as well as three-year overall, event-free and disease-free survival.
“This is an important study for pediatric patients with Ph+ and ABL-class Ph-like ALL, who have worse outcomes than the majority of our pediatric patients with B-ALL,” says Dr. Niswander. “It is our first large cooperative group trial designed to not only evaluate the combination of TKI with blinatumomab-containing chemo-immunotherapy backbone but also to use this more targeted approach to replace a block of traditional cytotoxic chemotherapy. We hope this strategy will lead to reduced long-term toxicities for these patients.”
BROADCASTMED