Safety of low-dose inotuzumab ozogamicin posttransplant in B-ALL: Phase I trial

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for adult and pediatric patients with acute lymphoblastic leukemia (ALL), relapse rates of 20−50% are still seen post-allo-HSCT, after which chemotherapeutic options are limited and the prognosis is poor.¹

Inotuzumab ozogamicin (InO) is a CD22-directed monoclonal antibody that has demonstrated significant activity in ALL. Here, we summarize results from a phase I multicenter study (NCT03104491) investigating the safety and feasibility of low-dose InO post-allo-HSCT in patients with high-risk B-cell ALL published by Metheny et al.¹ in Blood Advances.

Study design¹

• Included patients aged 16−75 years diagnosed with CD22⁺ ALL who were in complete remission at Day 30 post-allo-HSCT, and had a high risk of relapse.
• InO was given on Day 1 of each 28-day cycle at four dose levels: 0.3 mg/m², 0.4 mg/m², 0.5 mg/m², and 0.6 mg/m²
• The primary endpoint was to determine the maximum tolerated dose of InO.
• Secondary endpoints included safety, rate of sinusoidal obstruction syndrome, non-relapse mortality, 1-year progression-free survival (PFS) and overall survival rates post-allo-HSCT, and measurable residual disease (MRD) status after InO.

Key findings¹

Safety

• A total of 19 patients were enrolled in the study between July 31, 2017, and October 18, 2021.
• One dose-limiting toxicity was reported at the 0.5 mg/m² dose level due to prolonged thrombocytopenia.
• The maximum tolerated dose was 0.6 mg/m²
• No cases of sinusoidal obstruction syndrome were reported.
• The most common any-grade adverse events were thrombocytopenia (42%), neutropenia (32%), and nausea/vomiting (42%).

Survival and relapse

• Among the entire cohort, the 1-year PFS was 89%.
• There were two cases of relapse, one occurred seven months post-allo-HSCT and the other 23 months post-allo-HSCT.
• Four out of six patients converted from MRD-positivity to MRD-negativity after treatment with InO.
• The 1-year overall survival was 94%, and the 1-year non-relapse mortality was 5.6%.
• Acute graft-versus-host disease was reported in 72.2% of patients.
• New or chronic graft-versus-host disease was seen in 44.4%.

Key learnings
Low dose (up to 0.6 mg/m2) of InO posttransplant was well tolerated and feasible in patients with ALL at a high risk of relapse. Low-dose InO posttransplant was also associated with high PFS rates and low relapse rates. These data support the investigation of low-dose InO as maintenance therapy post-allo-HSCT in a phase II trial.