Outcomes with ponatinib in patients with relapsed/refractory Philadelphia-chromosome positive acute lymphoblastic leukemia: A systematic review and meta-analysis
Year: 2025
Type: conference-abstract
Abstract: Introduction: Outcomes in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) have improved significantly with the introduction of tyrosine kinase inhibitors (TKIs); however, relapse remains common, and resistance to first- and second-generation TKIs poses a major therapeutic challenge. Ponatinib, a third-generation TKI, has emerged as a viable option for patients with relapsed or refractory (R/R) Ph+ ALL. This systematic review and meta-analysis aimed to evaluate its clinical outcomes and safety profile in this setting. Methods: A systematic search was conducted in PubMed, Cochrane, Embase, Google Scholar, and ClinicalTrials.gov (from inception to May 2025) following PRISMA guidelines. Search terms included “Philadelphia-chromosome-positive acute lymphoblastic leukemia,” “relapsed/refractory,” and “Ponatinib.” After screening 529 references, five studies met the inclusion criteria: original research evaluating Ponatinib monotherapy in R/R Ph+ ALL with reported outcomes. Meta-analyses were conducted using a random-effects model for outcomes reported in two or more studies. Pooled prevalence estimates were reported with 95% confidence intervals (CIs), and heterogeneity was assessed using the I² statistic. Results: Five studies with a total of 469 participants were included: two retrospective, one prospective, one observational, and one post-marketing surveillance study. The median patient age was 56 years (range: 18–91), and 58% (n = 252) were male. Most had prior exposure to TKIs (96.5%, n = 443), and 28% (15/53) had undergone prior allogeneic hematopoietic stem cell transplantation (allo-HCT). The pooled complete remission (CR) rate was 86% (95% CI: 66–99%, I² = 29.5%), and the 1-year overall survival (OS) rate was 69% (95% CI: 64–73%, I² = 0.0%). Median overall survival ranged from 1.7 to 58.7 months across studies, and one study reported a 3-year progression-free survival rate of 48.9. The pooled rate for patients who underwent allo-HCT after Ponatinib was 27% (95% CI: 17–41%, I² = 0.0%). The pooled rate for non-responders to Ponatinib was 15% (95% CI: 2–34%, I² = 0.0%). The pooled adverse event (AE) rate was 53% (95% CI: 40–65%, I² = 47.9%). Commonly reported adverse events included thrombocytopenia (67%), neutropenia (44%), cytokine release syndrome (CRS) (11.5%), and immune effector cell-associated neurotoxicity syndrome (ICANS) (23%). Conclusion: Ponatinib appears to be an effective treatment option in relapsed/refractory Ph+ ALL, demonstrating favorable remission and 1-year survival outcomes with manageable toxicity. Further prospective trials with larger sample sizes and longer follow-up are needed to establish its optimal use and long-term efficacy.
Source: Blood
Authors: Hafiz Muhammad Hannan Javed, Muhammad Kashif Amin, Zeeshan Sattar, Mamoon Ahmed, Aman Ullah, Aminah Tayyab, Waleeh Ahmed Mir, Fatima Sial, Ruhma Sehar, Muhammad Umair Mushtaq, Moazzam Shahzad
Institutions: Peninsula Regional Medical Center, University of Kansas Medical Center, University of South Dakota, Saint Louis University Hospital, University of Oklahoma Health Sciences Center, King Edward Medical University, Allama Iqbal Medical College, University of South Florida, Moffitt Cancer Center
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417002702
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