Outcomes by Body Mass Index in Patients With B-Cell Precursor Acute Lymphoblastic Leukemia Treated with Inotuzumab Ozogamicin.

BACKGROUND: Inotuzumab ozogamicin (lnO) is approved for the treatment of adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Elevated body mass index (BMI) could be associated with worse outcomes. OBJECTIVE: To conduct post hoc BMI-stratified efficacy/safety analyses of lnO. PATIENTS AND METHODS: Pooled data from phase 1-4 InO trials were analyzed, with patients grouped by BMI: < 25 kg/m2 (normal), 25-30 kg/m2 (overweight), and > 30 kg/m2 (obese), including a subset of morbidly obese (> 40 kg/m2) patients. Descriptive analyses included efficacy, safety, and pharmacokinetic simulations for InO. RESULTS: Across 338 patients, complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 69.7%, 75.9%, 68.7%, and 84.6% patients in the < 25, 25-30, > 30, and > 40 kg/m2 subgroups, respectively. The 24-month probability of progression-free survival was 19.9%, 12.8%, 10.9%, and 23.1%; the 24-month overall survival probability was 28.1%, 22.1%, 17.5%, and 23.1% in these subgroups, respectively. Most deaths were due to progressive disease. Most patients experienced treatment-emergent adverse events (TEAEs), with similar incidence across subgroups. The most common grade ≥ 3 TEAE was neutropenia (36.1%), with sinusoidal obstruction syndrome (SOS) observed in 8.3%. 143 patients (42%) proceeded to hematopoietic stem cell transplant (HSCT) after lnO treatment, with 31 (21.7%) experiencing post-HSCT SOS; the BMI > 40 kg/m2 subgroup (n = 7 receiving HSCT) had the numerically highest post-HSCT non-relapse mortality. In simulations for dose capping (capped maximum dose), exposure metrics were similar across subgroups with/without dose capping. CONCLUSION: Efficacy/safety outcomes with InO were consistent across BMI subgroups. Dose-capping does not appear to be required.