Daniel J DeAngelo, Ying Chen, Ryan D Cassaday, Jennifer E Hibma, Derek Z Yang, May Garrett, Fan Zhang, Svetoslav H Dimitrov, Erik R Vandendries, Hagop M Kantarjian
Following the approval of inotuzumab ozogamicin (InO) monotherapy for the treatment of adults with relapsed/refractory CD22-positive acute lymphoblastic leukemia, the US Food and Drug Administration issued a post-marketing requirement study due to their concerns that the proposed dose of 1.8 mg/m2/cycle may not be optimal in balancing the safety and efficacy of InO. Here, we provide an overview of single-agent InO dose-optimization strategies, including the rationale for studying a fractionated InO dosing schedule and justification for the approved dosing regimen based on clinical safety and efficacy data, as well as comprehensive exposure-response analyses from InO clinical studies.