A multicenter study of posttransplant low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia.

The curative potential of allogeneic hematopoietic transplant (alloHCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible post alloHCT. Therefore we conducted a phase I study to determine the dose and safety in this setting. Patients were eligible if they were aged 16-75, had undergone alloHCT for CD22+ALL, were in complete remission (CR) after alloHCT, had high-risk of recurrence, were between day 40 and 100 post-alloHCT with adequate graft function, and did not have a history of hepatic veno-occlusive disease (VOD). The objectives of this trial were to define INO maximum tolerated dose (MTD), to determine the post alloHCT INO safety, and to measure one-year progression-free-survival (PFS). The trial design followed a 3+3 model. The treatment consisted of INO given on day 1 of 28-day cycles. Dose levels were 0.3mg/m2, 0.4mg/m2, 0.5mg/m2, and 0.6mg/m2. Median age was 44 years (range, 17-66; n=18). Disease status at transplant was first CR (n=14) or second CR or beyond (n=4). Preparative regimen was of reduced intensity in 72% of the transplants. Most common toxicity was thrombocytopenia. There were no instances of VOD; the MTD was 0.6mg/m2. One-year non-relapse mortality was 5.6%. With a median follow up of 18.1 months (8.6-59 months) one-year post-alloHCT PFS and OS is 89% and 94%, respectively. ClinicalTrials.gov Identifier: NCT03104491.