Evaluation of CD22 modulation as a mechanism of resistance to inotuzumab ozogamicin (InO): Results from central CD22 testing on the Children’s Oncology Group (COG) phase II trial of INO in children and young adults with CD22+ B-acute lymphoblastic leukemia (B-ALL).

Abstract

10519 Background: The COG AALL1621 phase 2 trial evaluated the efficacy of InO in children and young adults with relapsed/refractory CD22+ B-cell ALL. We report results of central surface CD22 expression on ALL and impact on response. Methods: Optional central CD22 testing was performed on bone marrow and/or peripheral blood at the NCI flow cytometry (FC) laboratory pre/post cycle 1. Percentage of blasts with CD22+ expression (CD22%) was measured by multiparameter FC and the BD Biosciences QuantiBRITE system quantified the CD22 site density by measuring CD22 antibody bound per cell (ABC). Comparison of ABC and CD22% between subgroups was based on Wilcoxon rank sum test or signed rank test as appropriate. Post-treatment CD22 assessments could only be performed on those with residual ALL. Results: Amongst 48 patients, 28 (58.3%) achieved a complete response (CR) or CR with incomplete count recovery. The median CD22 ABC, pre and post-cycle 1, was 2688 (range, 290-10715, n = 33) and 1098 (184-6822, n = 15) respectively. Amongst 27 subjects with paired pre/post samples, median pre-treatment CD22 ABC was lower in those with residual ALL (n = 13) than in those without residual ALL (ABC 1005 (290-8848) vs ABC 4123 (762-10715), p = 0.003). Baseline CD22% ranged more widely in those with residual ALL, median 99% (40-100%) vs. 99% (92.9-100%, no residual ALL) p = 0.025; and significant decreases in CD22% were seen compared to baseline in those with residual ALL, with median post-treatment CD22% 82% (1.4%-100%), p = 0.007. Amongst 3 subjects with baseline partial CD22% (40%, 79% and 83% partial CD22+ populations), post-cycle 1 evaluations revealed emergence of predominantly CD22 negative populations (6.5%, 34% and 48% CD22+, respectively), precluding eradication of minimal residual disease. Amongst those with KMT2A rearrangement, 2 of 4 had partial CD22 expression and 4 of 4 had low ABC ( < 1500). Conclusions: Baseline CD22 expression, specifically low CD22 ABC and partial CD22% were significantly associated with response to treatment, emerging as potential biomarkers for poor InO response. This is particularly relevant to patients with KMT2Arearrangement who may be predisposed to CD22 partial positivity and low ABC. Evolution of CD22 negative/dim disease post-therapy suggests CD22 modulation is a mechanism of resistance to InO. Response to InO monotherapy may be limited in those with baseline CD22 negative/dim populations. Clinical trial information: NCT02981628.