Mechanisms of inotuzumab resistance in pediatric B-lymphoblastic leukemia (B-ALL).

Antigen escape has emerged as a major cause of post-immunotherapy relapses, especially in children with B-lymphoblastic leukemia (B-ALL). We sought to study the resistance mechanisms that contribute to antigen escape following treatment with CD22-directed therapies, such as inotuzumab, an antibody-drug conjugate. We analyzed 2 paired specimens from pediatric patients with relapsed B-ALL treated on COG AALL1621 with inotuzumab. Paired specimens were obtained at the timepoint of study enrollment and at the timepoint of subsequent relapse after inotuzumab treatment, and we performed transcriptome-wide RNA sequencing.