Research Information System
Haematologica, vol.110, no.8, pp.1736-1746, 2025 (SCI-Expanded)
Inotuzumab ozogamicin (InO) is approved for treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Previous studies reported higher rates of post-hematopoietic stem cell transplant (HSCT) hepatic sinusoidal obstruction syndrome (SOS) in patients receiving InO than in those receiving chemotherapy prior to HSCT. It is unknown whether a lower InO dose would reduce the risk of post-HSCT SOS or affect efficacy. This study evaluated efficacy and safety of the currently approved InO starting dose and a lower dose in adults with R/R ALL who were eligible for HSCT and were identified as being at higher risk of post-HSCT SOS. This open-label, phase IV study (NCT03677596) had two phases: in the run-in phase patients received InO at 1.2 mg/m2/cycle (N=22); in the randomized phase patients received InO starting at dose levels of 1.8 mg/m2/cycle (N=38) or 1.2 mg/m2/cycle (N=42). Primary endpoints were rate of SOS and rate of hematologic remission. Overall, SOS was reported in ten patients (9.8%) and in all cases was post-HSCT SOS. In patients who proceeded to HSCT, post-HSCT SOS rates were 20%, 28.6%, 25.8%, and 16.7% in 1.2 mg/m2/cycle (run-in), 1.2 mg/m2/cycle (randomized), 1.2 mg/m2/cycle (run-in and randomized), and 1.8 mg/m2/cycle (randomized) InO dosing subgroups, respectively. The rates of complete remission with or without complete hematologic recovery were 50.0%, 83.3%, 71.9%, and 68.4% in the respective subgroups. The study found that a starting dose of the 1.2 mg/m2/cycle demonstrated efficacy and safety consistent with those of the recommended 1.8 mg/m2/ cycle dose in adults with R/R ALL who were eligible for HSCT and had a higher risk of post-HSCT SOS.