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

The curative potential of allogeneic hematopoietic transplantation (allo-HCT) 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 signi ficant activity against ALL. We hypothesized that low -dose INO would be safe and feasible after allo-HCT. Therefore, we conducted a phase 1 study to determine the dose and safety in this setting. Patients were eligible if they were aged 16 to 75 years, had undergone allo-HCT for CD22 + ALL, were in complete remission (CR) after allo-HCT, had high risk of recurrence, were between day 40 and 100 after allo-HCT with adequate graft function, and did not have a history of sinusoidal obstruction syndrome (SOS). The objectives of this trial were to de fine INO maximum tolerated dose (MTD), to determine post -allo-HCT INO safety, and to measure 1 -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 0.3 mg/m 2 , 0.4 mg/m 2 , 0.5 mg/m 2 , and 0.6 mg/m 2 . Median age was 44 years (range, 17-66 years; n = 18). Disease status at transplantation was first CR (n = 14) or second CR or beyond (n = 4). Preparative regimen was of reduced intensity in 72% of patients who received transplantation. Most common toxicity was thrombocytopenia. There were no instances of SOS; the MTD was 0.6 mg/m 2 . One-year nonrelapse mortality was 5.6%. With a median follow-up of 18.1 months (range, 8.6-59 months) 1 -year post -allo-HCT PFS and overall survival is 89% and 94%, respectively. Low -dose INO has a favorable safety pro file and was associated with high rates of 1 -year PFS. This trial was registered at www.clinicaltrials.gov as #NCT03104491.