Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study

Abstract

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.