CD22low/Bcl-2high expression identifies poor response to inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia

• DOI: 10.1182/bloodadvances.2021006810
• Publication Date: 2022-05-02T21:32:27Z
• Authors: Astrid Wintering; Kenichi Ishiyama; Stanley Tamaki; Courtney Tamaki; Joshua Fandel; Lingyun Ji; Brent L. Wood; Nirali N. Shah; Constance M. Yuan; Maureen M. O’Brien; Mignon L. Loh; Ernesto Diaz-Flores
• Keywords: CD22; Refractory (planetary science); Antibody-drug conjugate; Minimal Residual Disease; Complete response

Outcomes for pediatric relapsed or refractory acute lymphoblastic leukemia (ALL) remain unsatisfactory. Administration of Inotuzumab ozogamicin (InO), a CD22-targeted antibody-drug conjugate, has shown remarkable activity but predictors response to InO with improved accuracy over CD22 expression and site density have not been reported. We analyzed 68 samples from 28 patients enrolled in Children's Oncology Group trial AALL1621 (NCT02981628) collected before after treatment InO. utilized B-ALL-centric CyTOF protein profiling approach. High-dimensional clustering analysis depicted distinct tumor profiles between complete partial responders. Our analyses identified frequencies CD22high cells CD22low/Bcl-2high as good poor response, respectively. Furthermore, residual blasts at end cycle 1 2 showed persistently high Bcl-2 family members. These data provide new insights into raise the potential inhibitors concurrent therapy these patients.