Photo Credit: Nemes Laszlo

The following is a summary of “Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab,” published in the May 2025 issue of Journal of Hematology & Oncology by Short et al. 

Researchers conducted a retrospective study to identify clinical and molecular features associated with relapse in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph + ALL) treated with chemotherapy-free regimens.  

They performed a phase II clinical trial involving 76 patients newly diagnosed with Ph+ ALL. Participants received between 12 and 15 doses of intrathecal chemotherapy for central nervous system (CNS) prophylaxis. The study analyzed relapse patterns as well as clinical and molecular factors predicting relapse.  

The results showed that with a median follow-up of 29 months, the estimated 3-year event-free survival (EFS) rate was 78%, and overall survival (OS) was 88% and 10 patients (13%) experienced relapse, with a median time to relapse of 18 months (range, 8–24 months), whereas, 6 relapses were confined to extramedullary sites, including 5 in the CNS and 1 in the peritoneum and lymph nodes. The CD19 expression remained high at relapse in all cases. Univariate analysis identified white blood cell count (WBC) ≥70 × 10⁹/L at diagnosis (sHR 8.86 [95% CI, 2.33–33.70]; P = 0.001), CNS involvement at diagnosis (sHR 6.87 [95% CI, 1.54–30.68]; P = 0.01), and VPREB1 deletion (sHR 4.06 [95% CI, 1.05–15.76]; P = 0.04) as risk factors for relapse. The WBC ≥70 × 10⁹/L was observed in 22% of the cohort and corresponded to a 53% cumulative incidence of relapse (CIR), compared with 6% CIR for those with lower WBC. IKZF1^plus genotype, BCR::ABL1 transcript type, and measurable residual disease kinetics did not significantly affect relapse risk. On multivariate analysis (MVA), high WBC at diagnosis was the sole factor significantly linked to relapse (sHR 16.29 [95% CI, 2.35–113.00]; P = 0.005).  

Investigators concluded that WBC count ≥70 × 10⁹ /L was a high-risk factor in Philadelphia chromosome–positive acute lymphoblastic leukemia treated with frontline blinatumomab and ponatinib and may outweigh baseline molecular prognostic indicators. 

Source: jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01709-y