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.

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 versus chemotherapy prior to HSCT. It is unknown if a lower InO dose would reduce risk of post-HSCT SOS or if it would impact 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 4 study (NCT03677596) had 2 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 10 patients (9.8%); all were 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), respectively. The CR/CRi rates were 50.0%, 83.3%, 71.9%, and 68.4% in the respective subgroups. The study found that a starting dose of 1.2mg/m2/cycle demonstrated consistent efficacy and safety to 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.