Inotuzumab Ozogamicin for Relapsed/Refractory Acute Lymphoblastic Leukemia in the Global Phase 3 INO-VATE Trial: Efficacy and Safety By Baseline CD22 Expression Level

Abstract

Abstract Introduction: CD22 is expressed in >90% of cases of B-cell acute lymphoblastic leukemia (ALL) making it an attractive target for the treatment of B-cell malignancies. Inotuzumab ozogamicin (InO), an anti-CD22 antibody conjugated to calicheamicin, has demonstrated significantly greater efficacy vs standard care (SC) therapies in patients with relapsed/refractory (R/R) ALL in the INO-VATE trial (Kantarjian et al, 2016). Herein, the efficacy and safety of InO vs SC in patients with baseline leukemic blast CD22 positivity ≥90% vs Methods: In this phase 3 trial (NCT01564784) completed on LSLV 04Jan2017, patients with R/R ALL (including ~15% in each arm with Philadelphia-positive ALL) due to receive salvage 1 or 2 therapy were randomized to InO (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 (investigator choice of fludarabine/cytarabine [Ara-C]/granulocyte colony-stimulating factor [FLAG], Ara-C + mitoxantrone, or high-dose Ara-C). Efficacy was assessed in the intent-to-treat (ITT) population; safety was assessed in all patients who received ≥1 dose of study drug. Central flow cytometry was used to assess minimal residual disease (MRD) negativity ( Results: 326 patients (InO, n=164; SC, n=162) were included in the ITT analysis population with both arms being well balanced for baseline characteristics. Most patients in both arms had high (≥90%) CD22 positivity at baseline (InO, 65%; SC, 57%), with only a small fraction exhibiting CD22 positivity Conclusion: At least 90% of blasts were CD22-positive in the majority of patients. The greatest benefit from treatment with InO was observed in those patients with CD22 positivity ≥90%, while statistical differences in PFS, DOR, and OS could not be shown in patients with CD22 positivity Download : Download high-res image (147KB) Download : Download full-size image Disclosures Kantarjian: Bristol-Meyers Squibb: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Delta-Fly Pharma: Research Funding; Pfizer: Research Funding. Stock: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy. DeAngelo: Glycomimetics: Research Funding; Amgen: Consultancy, Research Funding; Immunogen: Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Blueprint Medicines: Honoraria, Research Funding; Takeda Pharmaceuticals U.S.A., Inc.: Honoraria; Shire: Honoraria; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding; ARIAD: Consultancy, Research Funding; BMS: Consultancy; Celgene: Research Funding. Jabbour: Bristol-Myers Squibb: Consultancy. O'Brien: Gilead Sciences, Inc.: Consultancy, Other: Research Support: Honorarium, Research Funding; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Other: Research Support: Honorarium, Research Funding; Pfizer: Consultancy, Research Funding; ProNAI: Other: Research Support: Honorarium, Research Funding; Astellas: Consultancy; TG Therapeutics: Consultancy, Other: Research Support: Honorarium, Research Funding; GSK: Consultancy; Celgene: Consultancy; Acerta: Other: Research Support: Honorarium, Research Funding; Regeneron: Other: Research Support: Honorarium, Research Funding; AbbVie: Consultancy; Amgen: Consultancy; Sunesis: Consultancy; Aptose Biosciences, Inc.: Consultancy; Janssen: Consultancy; Vaniam Group LLC: Consultancy; Alexion: Consultancy. Wang: Pfizer: Employment, Equity Ownership. Paccagnella: Pfizer: Employment. Nguyen: Navigate BioPharma Services, INC: Employment. Sleight: Pfizer: Employment, Equity Ownership. Vandendries: Pfizer: Employment, Equity Ownership. Laird: Pfizer: Employment. Advani: Takeda/ Millenium: Research Funding; Pfizer: Consultancy.