Efficacy and safety of combination therapy of ponatinib and blinatumomab in Philadelphia chromosome positive acute lymphoblastic leukemia (ALL): A meta-analysis

Summary: Abstract Body: Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph+ALL) comprises 20-30% of adult ALL cases worldwide, characterized by aggressive progression and high mortality.Common symptoms include fatigue, fever, bruising, and recurrent infections. While combining tyrosine kinase inhibitors (TKIs)with chemotherapy has improved outcomes, it also presents significant toxicity. Recently, ponatinib, a third-generation TKI, and blinatumomab, a bispecific T-cell engager, have shown potential to improve survival and reduce toxicity. This study evaluates their efficacy and safety in Ph+ ALL treatment. A systematic review and meta-analysis was conducted using PubMed,Embase,Scopus, and Cochrane databases,including literature up to December 2024.Seven studies with 338 patients (294 newly diagnosed and 44 refractory cases, mean age 52.43 years,SD 15.21) met predefined criteria.Data were analyzed using OpenMeta software,with prevalence rates pooled under a random effects model. Heterogeneity was assessed using I2andχ2,with I2 > 50% indicating significant heterogeneity.Results showed an event-free survival rate of 0.62 (95% CI 0.35-0.89, I2=94.15%, P<0.01), hematologic response of 0.51(95%CI 0.26-0.75,I2=96.99%,P<0.01), and measurable residual disease negativity of 0.78 (95% CI 0.67-0.89, I2=75.91%,P=0.006).Overall survival reached 0.84(95%CI 0.75-0.93,I2=79.7%,P<0.01), relapse rates were 0.11 (95% CI 0.03-0.19,I2=82%,P<0.01), and complete molecular response was 0.87(95% CI 0.79-0.96,I2=76.06%, P<0.01). Adverse events across grades 1-4 were 0.16(95% CI 0.05-0.28, I2=77.51%, P=0.004).This analysis suggests ponatinib and blinatumomab can achieve improved survival, molecular responses, and low relapse rates within 24 months with manageable toxicity. Further large-scale studies are needed to confirm these findings and establish this combination as a standard therapy for Ph+ALL. Balakrishnan Kamaraj¹, Hrithik Dakssesh Putta Nagarajan¹, Subash Ganesan¹, Gurunathan Srinivasan³, parth mukeshbhai dhamelai², Aswath Sreeman Saravanan¹ 1. Madurai Medical College, Madurai, TN, India. 2. Maulana Azad Medical College, New Delhi, DL, India. 3. Stanley Medical College, Chennai, TN, India. Adaptive and Auto-Immunity