A real world study of inotuzumab ozogamicin for the treatment of B-cell acute lymphoblastic leukemia: Multi-center result from SH-ALL group

Abstract Background： Inotuzumab ozogamicin(INO) is an antibody-drug conjugate for CD22-positive acute B-cell lymphoblastic leukemia(B-ALL). INO has been available in China since June 2022, however, it lacks published data of INO from China. Herein, we present the clinical outcomes of INO-based treatment for adult B-ALL patients (pts) in our real-world study from Shanghai Acute Lymphoblastic Leukemia (SH-ALL) Research Group. Methods： In this retrospective real-world multi-center study, B-ALL pts treated by INO-based therapy within 8 centers of SH-ALL Research Group were analyzed. Pts received INO monotherapy or INO-based combined therapy. All Ph positive (Phpos) ALL pts received TKI. CD22 positivity is defined as CD22 expression ≥20% by multiparameter flow cytometry (MFC). Efficacy evaluation was assessed after 1 cycle of INO-based therapy. Minimal residual disease (MRD) is routinely monitored by MFC with a sensibility of 10-4. Adverse events (AEs) were assessed according to CTCAE v5.0. Results: From June 2022 to July 2025, a total of 102 pts with B-ALL received INO-based therapy in 8 centers in Shanghai, among whom 93 pts with available data were analyzed. The median age was 57 years old (range, 17-77). There were 23 (24.7%) Phpos pts and 70(75.3%) Ph negative (Phneg) pts. Before INO initiation, 3 pts were newly diagnosed (ND), 9 pts were on CR (3 MRD negative, 6 MRD positive) and 81(87.1%) pts were in relapsed/refractory (R/R) status. Among 70 Phneg pts, 21 pts received INO+venetoclax (VEN). Among 23 Phpos pts, besides TKI+INO combination, 12 pts received VEN additionally. Once CR or MRD negativity reached, eligible pts received allogeneic hematopoietic stem cell transplantation (allo-HSCT). After 1 cycle, CR rate and MRD negative rate were both 100% in 3 ND Phneg pts treated by INO+VEN. Among 6 MRD positive CR pts (3 Phneg and 3 Phpos), all pts but 1 Phneg pt with TP53 mutation reached MRD negativity (83.3%). For 81 R/R pts, 65(80.2%) pts reached CR. In 65 R/R pts who achieved CR, 63 pts had evaluable MRD, the MRD negative rate was 77.8% (49/63). Among all R/R pts, there were 61 Phneg and 20 Phpos pts. There was no significant difference neither in CR rate (82.0% vs 75.0%, p=0.526) nor in MRD negative rate (75.0% vs 86.7%, p=0.486) between Phneg and Phpos pts. In 81 R/R pts, 26 received INO+VEN regimen, in whom the CR rate was higher than that of pts received INO + other combination (92.3% vs 74.5%, p=0.07). The MRD negative rate of INO+VEN was also higher than INO + other combination (86.7% vs 75.0%, p=0.215). Up to August 2025, the median follow-up time was 6 months, median Overall Survival (OS) was not reached. The 6-months OS was 83.6% (95%CI 75.8%~92.3%). All 3 ND pts are alive in persistent remission. As for 9 CR pts, only 1 pt with persistent MRD after INO treatment died of disease progression. Among 81 R/R pts, the 6-months OS was 83.2% (95%CI 74.9%~92.4%), 60 Phneg pts had significant better survival than 21 Phpos pts (87.2% vs 69.4%, p=0.0473). The safety profiles of the INO-based therapy were acceptable. Non-hematological AEs were primarily G1-2, reversible rapidly after symptomatic management. Veno-occlusive disease (VOD) occurred in 4 pts: 2 pts during INO treatment, and 2 pts after allo-HSCT. Most of the G3-4 AEs were hematological AEs, especially thrombocytopenia. No treatment-related mortality was observed. Conclusion Here, we first reported the real-world multi-center outcomes of INO-based treatment from SH-ALL research group. In this large cohort, we confirmed the efficacy and safety of INO in B-ALL pts with different tumor burdens. The combination of INO+VEN showed higher CR rate and MRD negative rate. These findings will be further validated through a prospective study.