Olverembatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: Meta-analysis of efficacy and safety outcomes.

Abstract

e18503 Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is an aggressive B-cell malignancy with substantial relapse risk despite tyrosine kinase inhibitors (TKIs). Olverembatinib is a third-generation TKI with promising activity in CML and Ph+ ALL, particularly in T3151-mutated disease. We hereby report results of a meta-analysis evaluating the safety and efficacy of Olverembatinib. Methods: This is a meta-analysis aimed to systematically evaluate the efficacy outcomes (response rates) and safety profile of Olverembatinib in adolescent and adult patients with Ph+ ALL, integrating evidence from interventional trials and observational studies. A systematic literature search was conducted from database inception through October 2025 across PubMed, Scopus, Web of Science, and Cochrane Library to identify eligible studies (inclusion criteria: human subjects with Ph+ ALL; exclusion criteria: preclinical, single-case, non-English, and review studies). Proportions for objective response rate (ORR), complete response (CR), partial response (PR), minimal residual disease (MRD) negativity, and adverse events (AEs) were stabilized using Freeman-Tukey double arcsine transformation and pooled with inverse variance weighting. Between-study heterogeneity was estimated with DerSimonian-Laird method for τ 2 , with confidence intervals for τ 2 and τ derived via Jackson approach. Multiple meta-regression was utilized to assess moderator variables. Results: Fourteen studies were included; 7 clinical trials and 7 observational studies. Data from 253 patients were used for the efficacy analysis, and 320 were used for the safety analysis. Random-effects pooled estimates: ORR = 99.0% (95% CI: 94.0–100.0); CR = 96.0% (95% CI: 89.0–100.0); PR = 3.0% (95% CI: 0.0-15.0); MRD negativity at 1 month = 84.0% (95% CI: 59.0–99.0); complete molecular response (CMR) at 3 months = 84.0% (95% CI: 67.0–96.0). Meta-regression showed that median age significantly moderated ORR (p = 0.001), whereas study design and publication year did not (p > 0.05). Safety outcomes included any AE = 79.0% (95% CI: 64.0–91.0), severe AE = 34.0% (95% CI: 19.0–51.0), grade ≥3 neutropenia = 25.0% (95% CI: 6.0–49.0), and grade ≥3 infection = 14.0% (95% CI: 6.0–23.0), and discontinuation = 0.60% [95% CI: 0.00-2.90]. Conclusions: Olverembatinib achieved very high remission rates and molecular responses in Ph+ ALL, with MRD and CMR endpoints indicating rapid and durable disease control. Despite frequent hematologic and infectious toxicities, treatment discontinuation was rare, supporting a manageable safety profile.