BETHESDA, MD—While most blood cancers affect people in their later years, B-cell acute lymphoblastic leukemia (B-ALL) strikes at a much earlier age. It is the most common hematologic malignancy in adults under the age of 40, the age range of 80% of U.S. servicemembers.
Even as survival rates for most cancers have improved in recent years, the rates for leukemias affecting young adults have plateaued since the 1990s, with the 5-year survival rate with B-ALL for those over age 20 holding at approximately 40%, even as disease-free survival rates for children with B-ALL exceed 90%.
Recent research indicates that adults under 40 with B-ALL have better outcomes when they are treated following pediatric rather than adult protocols, which explains why Wanda Salzer, MD, of the Uniformed Services University joined forces with researchers at leading pediatric hospitals across the country to try to improve the results for a particularly challenging group of B-ALL patients.
About 3% of children with B-ALL have Philadelphia chromosome-like (Ph-like) B-ALL with an ABL-class fusion in ABL1, ABL2, PDGFRB or CSF1R but lack the chimeric gene BCR::ABL1, but among adults aged 21 to 39, this subtype of ALL accounts for 26% of cases. These patients are more likely to be male and have poorer outcomes than those with other B-ALL subtypes, indicating that new treatment strategies may be appropriate.
These B-ALL patients are predicted to respond to Bruton tyrosine kinase (BTK) inhibitors. On Dec. 11, Salzer presented results from a study that incorporated the BTK inhibitor dasatinib in post-induction therapy for patients with newly diagnosed ABL-class fusion B-ALL in an effort to boost survival rates at the 65th American Society of Hematology Annual Meeting in San Diego.
Twenty-two patients with B-ALL with ABL-class fusions (all under age 30) were assigned to receive dasatinib as part of a larger study of B-ALL. Of those, 77% were male. Twenty of the 22 had elevated end of induction minimal residual disease of 0.01% or greater and 6 of 10 with available results had end of consolidation minimal residual disease (MRD) of 0.01% or more.
Significantly, only 5 patients finished the prescribed protocol, even though dasatinib was well tolerated. Discontinuations occurred because of induction failure in two cases, relapse or switch to alternate therapy in one case each, one instance of death and 10 cases where it was determined to be in the patient’s best interest. Two patients discontinued for unknown reasons.
Compared to all patients in the study, the ABL-fusion group had four-year disease-free survival rates of 52.5 +18.1% versus 86.8+0.7% (p<0.0001) and overall survival of 79.4+13.6% versus 89.2+0.4% (p<0.0001).
Given the high discontinuation rate and early treatment failures associated with dasatinib, the researchers concluded that alternate strategies are needed.
- Salzer WL, Burke MJ, Devidas M, Chen Z, et. al. Feasibility and Outcome of Post-Induction Therapy Incorporating Dasatinib for Patients with Newly Diagnosed ABL-Class Fusion B-Lymphoblastic Leukemia (ABL-class Fusion B-ALL): Children’s Oncology Group AALL1131. Abstract 961. ASH 2023. Dec. 11, 2023.
