Jabbour E, et al. - The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. Herein, the efficacy, as well as safety of inotuzumab ozogamicin plus low-intensity chemotherapy for R/R, ALL was assessed. Inotuzumab + low-intensity mini–hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m² × 4 doses) chemotherapy provided encouraging outcomes in R/R ALL. Carefully considering VOD risk was recommended for patients with previous liver damage and among transplant candidates.

• Researchers carried out this single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center, Houston.
• Study participants were adults with R/R B-cell ALL.
• The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini–hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m² × 4 doses).
• Researchers administered inotuzumab on day 3 of the first 4 courses at 1.8 to 1.3 mg/m² for cycle 1 followed by 1.3 to 1.0 mg/m² for subsequent cycles.
• Overall response rate and overall survival (OS) were the primary end points.
• Safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate were included as secondary end points.

• In this study, a total of 59 patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated.
• Response was apparent in 46 patients (78%), 35 of them (59%) achieved complete response.
• Among responders, the observed overall MRD negativity rate was 82%.
• ASCT was performed in 26 patients (44%).
• Prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8) were the observed grade 3 to 4 toxic effects.
• In addition, occurrence of veno-occlusive disease (VOD) was reported in 9 patients (15%).
• Findings showed that, with a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively.
• Researchers noted that the 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P=.03).