Exploration of Potential Relationships between CD22 and Selected Safety Outcomes in the Inotuzumab Ozogamicin Phase 3 INO-VATE Study

Introduction: CD22 is widely expressed on leukemic lymphoblasts in patients with B-cell acute lymphoblastic leukemia (ALL). Inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody conjugated to calicheamicin, has shown significantly higher remission rates than standard of care (SC) chemotherapy in relapsed or refractory B-cell (R/R) ALL, independently of CD22 expression level. Here we report safety outcomes by CD22 expression in patients with R/R ALL receiving InO (vs SC) as salvage therapy in the INO-VATE trial (NCT01564784). Methods: Adults with CD22-positive ALL in 1st or 2nd salvage were randomized to InO (n=164; starting dose 1.8 mg/m2/cycle [0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21-28 day cycle for ≤6 cycles]) or SC (n=162; fludarabine/high-dose (HD) cytarabine (Ara-C)/granulocyte colony-stimulating factor, Ara-C plus mitoxantrone, or HD Ara-C).The InO dose was reduced to 1.5 mg/m2 per cycle in patients who achieved complete remission [CR] or CR with incomplete hematologic recover [CRi]. Last patient visit was January 4, 2017. Central flow cytometry was used to assess CD22 expression, which was quantified as % leukemic blasts CD22-positive and as Molecules of Equivalent Soluble Fluorochrome (a quantitative measure of receptor density on leukemic blasts [MESF]). Outcomes were reported in patients by baseline leukemic blast positivity (≥90% vs Results: At baseline, 142 InO patients and 117 SC patients had an evaluable sample for central-lab CD22 analysis. The majority of patients in both arms had high (≥90%) CD22 positivity (InO, 75.4%; SC, 72.6%), with a smaller proportion of patients exhibiting CD22 positivity Conclusions: The risk of developing TEAEs, including hepatic adverse events, which were more common in the InO vs SC arm, was not associated with intensity of CD22 expression in either the InO or SC arm. Among InO patients with post-treatment SCT, there was no apparent relationship between CD22 expression and the risk of developing VOD, when analyzing CD22 by % positivity or by MESF. Disclosures DeAngelo:BMS: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria; Pfizer Inc: Consultancy, Honoraria; Shire: Honoraria; Takeda: Honoraria; Blueprint Medicines: Honoraria, Research Funding; ARIAD: Consultancy, Research Funding; Amgen: Consultancy; Glycomimetics: Research Funding; Incyte: Consultancy, Honoraria. Advani:Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy. O9Brien:Sunesis: Consultancy, Research Funding; Acerta: Research Funding; Pfizer: Consultancy, Research Funding; Aptose Biosciences Inc.: Consultancy; GlaxoSmithKline: Consultancy; Amgen: Consultancy; Gilead: Consultancy, Research Funding; Astellas: Consultancy; Alexion: Consultancy; Abbvie: Consultancy; Kite Pharma: Research Funding; Celgene: Consultancy; Janssen: Consultancy; Vaniam Group LLC: Consultancy; Pharmacyclics: Consultancy, Research Funding; Regeneron: Research Funding; TG Therapeutics: Consultancy, Research Funding. Marks:Novartis: Consultancy; Pfizer: Consultancy; Amgen: Consultancy. Kantarjian:Orsenix: Honoraria; Novartis: Research Funding; Immunogen: Honoraria; BMS: Honoraria, Research Funding; Astex: Research Funding; ARIAD: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Actinium: Honoraria; AbbVie: Honoraria; Pfizer: Honoraria, Research Funding. Wang:Pfizer: Employment, Equity Ownership. Vandendries:Pfizer: Employment, Equity Ownership. Laird:Pfizer: Employment, Equity Ownership. Nick:Pfizer: Employment, Equity Ownership. Stelljes:Amgen: Honoraria; MSD: Consultancy; JAZZ: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria.