Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the INO-VATE Trial: CD22 Pharmacodynamics, Efficacy, and Safety by Baseline CD22.

Abstract

We assessed the relationship between cluster of differentiation-22 (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care (SC) in INO-VATE (NCT01564784). Adults with relapsed/refractory B-cell precursor CD22-positive (by local or central laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin (n = 164) or SC (n = 162). Outcomes were analyzed by baseline CD22 positivity (percentage of leukemic blasts CD22 positive, ≥90% vs. <90%) and CD22 receptor density [molecules of equivalent soluble fluorochrome (MESF), quartile analysis]. Most patients had high (≥90%) CD22 positivity per central laboratory. The response rate was significantly higher with inotuzumab ozogamicin versus SC. Minimal/measurable residual disease negativity, duration of remission (DoR), progression-free survival, and overall survival (OS) were significantly better with inotuzumab ozogamicin versus SC in patients with CD22 positivity ≥90%. Fewer patients had CD22 positivity <90%; for whom, response rates were higher with inotuzumab ozogamicin versus SC, but DoR and OS appeared similar. Similar trends were evident in quartile analyses of CD22 MESF and CD22 positivity per local laboratory. Among inotuzumab ozogamicin-responding patients with subsequent relapse, decrease in CD22 positivity and receptor density was evident, but not the emergence of CD22 negativity. Rates of grade ≥3 hematologic adverse events (AEs) were similar and hepatobiliary AEs rate was higher for inotuzumab ozogamicin versus SC. No apparent relationship was observed between the rates of hematologic and hepatic AEs and CD22 expression. Inotuzumab ozogamicin demonstrated a favorable benefit-risk profile versus SC in patients with higher and lower CD22 expression. Patients with high CD22 expression and normal cytogenetics benefited the most from inotuzumab ozogamicin therapy.