Inotuzumab Ozogamicin Post-Transplant for Acute Lymphoblastic Leukemia

Abstract

<h3>Background</h3> Allogeneic transplant (alloHCT) is a curative therapy for patients with acute lymphocytic leukemia (ALL). The curative potential of alloHCT is hampered by relapse, which is the major cause of treatment failure. Overall, relapse rates for these patients are in the range of 30% to 50% with the majority of these relapses occurring within the first year after alloHCT. Currently, there is no standard post-transplant therapy for patients with ALL. Inotuzumab ozogamicin (INO) is a CD22 monoclonal antibody bound to calicheamicin which has been shown to have significant activity against relapsed ALL. We hypothesize that low dose post-alloHCT maintenance therapy of INO will be safe and will reduce relapse rates after alloHCT for ALL. <h3>Methods</h3> Eligibility included patients aged 16-75 who have undergone alloHCT for CD22+ALL, have a high risk for relapse, have adequate graft and organ function, are between day 40 and 100 post-transplant, do not have active grade III/IV GVHD or any active GVHD of the liver, and have no history of veno-occlusive disease (VOD). The primary objective of this phase I clinical trial is to define a post alloHCT maximum tolerated dose (MTD) of INO. Secondary objectives include describing the safety profile of INO post-alloHCT, determining the rate of VOD, disease free survival (DFS) and overall survival (OS) at 1 year post alloHCT. The trial design is a 3+3 model. The study treatment consists of a total of four 28 day cycles of INO starting at dose level 0 (0.3mg/m2) given on day 1. Dose limiting toxicities (DLT) include VOD, prolonged cytopenia (more than 28 days), and death. If there are no DLTs experienced in a cohort, patients may be enrolled in the next highest dose level (Table 1). <h3>Results</h3> As of October 1st, 2019, 9 patients have been treated. One patient went off treatment after 1 cycle of INO (patient choice), two went off treatment after 3 cycles of INO (patient choice and physician choice) and one experienced a DLT due to prolonged thrombocytopenia. We have completed 1 year post-transplant follow up on 5 patients. All patients are alive and in CR. No patients experienced VOD. Significant side effects include thrombocytopenia and neutropenia. The percentage of any aGVHD is 62.5% and the rate of grade III/IV aGVHD is 0%. The percentage of any cGVHD is 42.8%. Patient characteristics are described below (Table 2). <h3>Conclusions</h3> In this phase 1 study, INO at doses of 0.3 and 0.4mg/m2 was well tolerated. Thrombocytopenia may be the dose limiting toxicity. The absence of disease recurrence in this small cohort of high risk ALL patients is very promising.