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

摘要: Introduction: CD22 is expressed in >90% of cases B-cell acute lymphoblastic leukemia (ALL) making it an attractive target for the treatment malignancies. Inotuzumab ozogamicin (InO), anti-CD22 antibody conjugated to calicheamicin, has demonstrated significantly greater efficacy vs standard care (SC) therapies patients with relapsed/refractory (R/R) ALL INO-VATE trial (Kantarjian et al, 2016). Herein, and safety InO SC baseline leukemic blast positivity ≥90% Methods: In this phase 3 (NCT01564784) completed on LSLV 04Jan2017, R/R (including ~15% each arm Philadelphia-positive ALL) due receive salvage 1 or 2 therapy were randomized (1.8 mg/m2/cycle [0.8 mg/m2 day 1; 0.5 days 8 15 a 21-28 cycle ≤6 cycles]) (investigator choice fludarabine/cytarabine [Ara-C]/granulocyte colony-stimulating factor [FLAG], Ara-C + mitoxantrone, high-dose Ara-C). Efficacy was assessed intent-to-treat (ITT) population; all who received ≥1 dose study drug. Central flow cytometry used assess minimal residual disease (MRD) negativity ( Results: 326 (InO, n=164; SC, n=162) included ITT analysis population both arms being well balanced characteristics. Most had high (≥90%) at 65%; 57%), only small fraction exhibiting Conclusion: At least 90% blasts CD22-positive majority patients. The greatest benefit from observed those ≥90%, while statistical differences PFS, DOR, OS could not be shown Disclosures Kantarjian: Bristol-Meyers Squibb: Research Funding; ARIAD: Amgen: Novartis: Delta-Fly Pharma: Pfizer: Funding. Stock: Consultancy, Membership entity9s Board Directors advisory committees; Seattle Genetics: Consultancy. DeAngelo: Glycomimetics: Immunogen: Honoraria, Incyte: Honoraria; Blueprint Medicines: Takeda Pharmaceuticals U.S.A., Inc.: Shire: Pfizer Novartis Corporation: BMS: Consultancy; Celgene: Jabbour: Bristol-Myers O9Brien: Gilead Sciences, Other: Support: Honorarium, CLL Global Foundation: Pharmacyclics: ProNAI: Astellas: TG Therapeutics: GSK: Acerta: Regeneron: AbbVie: Sunesis: Aptose Biosciences, Janssen: Vaniam Group LLC: Alexion: Wang: Employment, Equity Ownership. Paccagnella: Employment. Nguyen: Navigate BioPharma Services, INC: Sleight: Vandendries: Laird: Advani: Takeda/ Millenium: