Outcomes with dasatinib in Philadelphia Chromosome–Positive acute lymphoblastic leukemia: A systematic review and meta-analysis

Abstract

Abstract Introduction: Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) is a high-risk leukemia subtype with limited long-term survival. While imatinib has improved remission rates, resistance often develops. Dasatinib, a second-generation tyrosine kinase inhibitor (TKI), has shown activity across treatment phases. This systematic review and meta-analysis evaluated outcomes of dasatinib monotherapy in Ph+ ALL. Methods: A systematic search was conducted in PubMed, Cochrane, Embase, Google Scholar, and ClinicalTrials.gov (inception to May 2025), following PRISMA guidelines. Search terms included “Philadelphia-chromosome-positive acute lymphoblastic leukemia” and “Dasatinib.” From 529 references, 10 studies were included based on predefined criteria: dasatinib monotherapy in Ph+ ALL with reported outcomes. Meta-analyses were conducted for outcomes reported in ≥2 studies using a random-effects model. Pooled prevalence estimates and 95% confidence intervals (CIs) were reported. Statistical heterogeneity was assessed using the I² statistic, and all analyses were performed using RevMan version 5.4. Results: A total of 571 patients were analyzed from 10 studies (6 phase II, two retrospective, one phase I, and one phase I/II). The median age was 52.5 years (range, 14–87), with males accounting for 54% (n = 310). Most patients (n = 356; 62%) received dasatinib in the frontline setting, 23% (n = 133) had relapsed or refractory disease, and 14% (n = 82) received it post-allo-hematopoietic stem cell transplantation as maintenance. Among evaluable studies, the median peripheral white blood cell (WBC) count was 12.5 × 10⁹/L (range, 0.1–443), and the median bone marrow blasts were 89% (range, 0–100). Prior allogeneic hematopoietic stem cell transplantation was reported in 31% (n = 47/150). The pooled complete remission (CR) rate was 94% (95% CI: 0.91–0.96, I² = 77%), and partial remission (PR) was 14% (95% CI: 0.08–0.21, I² = 0%). Complete molecular response (CMR) was achieved in 38% (95% CI: 0.33–0.43, I² = 96%) and disease-free survival (DFS) in 42% (95% CI: 0.33–0.50, I² = 16%). The pooled rate for relapse/refractory disease after Disatinib was 34% (95% CI: 0.28–0.40, I² = 79%). Pooled overall survival was 61% at 3 years (95% CI: 0.54–0.69, I² = 94%) and 41% at 5 years (95% CI: 0.33–0.50, I² = 53%). Treatment-related adverse events included tumor lysis syndrome in 8% (95% CI: 0.04–0.12, I² = 81%), neutropenia in 62% (95% CI: 0.56–0.67, I² = 97%), and thrombocytopenia in 63% (95% CI: 0.57–0.70, I² = 75%). Conclusion: Dasatinib monotherapy achieves high remission rates with manageable toxicity in Ph+ ALL across frontline, salvage, and maintenance settings. Despite this, modest molecular response and long-term survival reinforce the need for optimized combination strategies and prospective trials.