Efficacy and Safety of Inotuzumab Ozogamicin and Its Combination Therapies in Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis

Changtao Lao¹Jiange Wen²Yuezhen Wen^1*

• ¹Shenzhen Hospital, Peking University, Shenzhen, Beijing Municipality, China
• ²Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, China

Background: Although treatment for acute lymphoblastic leukemia (ALL) has advanced considerabl y, adults with relapsed or refractory (R/R) disease continue to face a grave prognosis. Inotuzumab oz ogamicin (InO), a CD22-directed antibody-drug conjugate, represents a promising development for B -cell ALL. This systematic review and meta-analysis aims to define the precise efficacy and safety pr ofile of InO-based therapies—both monotherapy and combination regimens—in adults with newly di agnosed and R/R ALL. Methods: A systematic literature search was conducted in PubMed, Web of Science, Embase, the Co chrane Library, and clinical trial registries through December 2, 2024. The primary outcomes were o verall response (OR), complete remission (CR), minimal residual disease (MRD) negativity, overall s urvival (OS), and the rate of stem cell transplantation (SCT). Secondary outcomes comprised adverse events (AEs) and relapse. Results: The meta-analysis included 1 randomized controlled trial (RCT), 14 single-arm studies, and 1 clinical trial, encompassing 1,068 patients. The pooled efficacy outcomes were as follows: OR rate: 89.0% (95% Confidence interval (CI): 85.8%-92.2%, 95% Prediction interval (PI): 1.2%-99.9%; I² = 90.1%, P < 0.001), CR rate: 70.5% (95% CI: 58.6%-82.5%, 95% PI: 3.3%-76.9%; I²=94.0%, P < 0.0 01), MRD-rate: 84.6% (95% CI: 79.5%-89.6%, 95% PI: 0.4%-99.8%; I²=80.9%, P < 0.001), 1-year OS rate: 61.7% (95% CI: 44.9%-78.5%; I² = 94.1%, P < 0.001), 2-year OS rate: 51.4% (95% CI: 32. 2%-70.7%; I² = 93.8%, P < 0.001), 3-year OS rate: 46.9% (95% CI: 22.5%-71.4%, 95%; I² = 95.2%, P < 0.001), 5-year OS rate: 44.9% (95% CI: 39.2%-50.5%, 95%; I² = 0.0%, P=0.482), SCT rate: 27. 5% (95% CI: 16.6%-38.4%, 95% PI: 1.2%-79.4%; I²=95.2%, P < 0.001), relapse rate: 23.6% (95% C I: 16.6%-30.6%, 95% PI: 16.6%-99.6%; I²=78.2%, P <0.001), and incidence of veno-occlusive dise ase (VOD): 6.2% (95% CI: 3.8%-8.6%, 95% PI: 6.6%-54.5%; I²=68.0%, P < 0.001). Conclusion: InO demonstrates significant efficacy and a manageable safety profile in adult patients with ALL, supporting its use as a viable therapeutic option. Further randomized studies are needed to validate these findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024619042.