Low SOS/VOD Risk with Inotuzumab Ozogamicin as a Bridging Strategy to Second Allogeneic HSCT: A Real-World Study in...

Relapse of B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major clinical challenge, and the use of inotuzumab ozogamicin (InO) as a bridge to second (2nd) HSCT is often constrained by concerns regarding sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). We retrospectively analyzed 25 patients with post-allo-HSCT relapsed or persistent MRD-positive B-ALL treated with InO. The primary objective was to assess SOS/VOD risk and safety of InO as a bridging strategy to 2nd allo-HSCT, with secondary endpoints including response, survival, and transplant outcomes. Among 13 morphologic relapse patients, 10 (76.9%) achieving complete remission (CR), and 11 (91.6%) of 12 MRD-positive patients converting to MRD negativity. Nine patients (36%) proceeded to 2nd allo-HSCT, including two with persistent disease. Notably, no cases (0%) of SOS/VOD were observed. Hepatic safety analysis demonstrated that most patients maintained normal bilirubin levels (median 11.3 μmol/L), with only one case of severe hyperbilirubinemia attributable to pre-existing hepatic aGVHD. AST/ALT elevations were predominantly grade 1-2, with no grade ≥3 events, and all abnormalities resolved with supportive care. Total of 68% of patients received reduced or intermediate InO doses (.80 to 1.3 mg/m²), and HSCT was performed after individualized conditioning strategies. With a median follow-up of 348 days (range, 26 to 1219), patients bridged to 2nd allo-HSCT demonstrated higher 2-year overall survival (OS) and leukemia-free survival (LFS) than those who did not (OS: 53.6% versus 38.9%; LFS: 53.6% versus 31.7%; both P > .05), along with a lower 2-year cumulative incidence of relapse (14.3% versus 52.4%; P = .153), and a slightly higher nonrelapse mortality (NRM) rate (22.2% versus 18.8%). All transplanted patients achieved successful engraftment, and the incidence of grade III to IV acute GVHD was 11.1%, moderate-to-severe chronic GVHD occurred in 33.3% of patients. In this real-world cohort, InO enabled quick disease control and safe transition to 2nd allo-HSCT, with an unexpectedly absent incidence of SOS/VOD. These findings suggest that, with optimized dosing and transplant strategies, the hepatotoxic risk of InO may be substantially mitigated. The principal clinical value of InO in this setting lies in facilitating access to potentially curative transplantation.