Inotuzumab ozogamicin (InO), an investigational anti-CD22 antibody drug conjugate, demonstrated a higher complete hematologic remission rate in adult patients with relapsed or refractory CD22-positive acute lymphocytic leukemia (ALL), compared with rates achieved with standard-of-care chemotherapy.
ALL is an aggressive form of leukemia with a poor prognosis in adults, a poor cure rate (20-40%), and a “dismal” five-year overall survival rate for relapsed/refractory disease, study co-author Daniel J. DeAngelo, MD, PhD, of Dana-Farber Cancer Institute, told ASH Clinical News.
The majority of cases of B-cell ALL express CD22, a protein that prevents the over-activation of the immune system. InO, which works by binding to the CD22 antigen on malignant B cells, where the cytotoxic agent calicheamicin is released to destroy the cell, had shown initial efficacy in previous studies.
The 326 patients enrolled in the open-label, randomized phase III trial were administered InO intravenously once a week for three weeks, in a three- to four-week cycle, for up to six cycles. Chemotherapy options in the standard-of-care (SOC) arm included fludarabine, cytarabine, and G-CSF; high-dose cytarabine; or cytarabine and mitoxantrone.
The study had dual primary endpoints – complete remission (CR) or CR with incomplete hematologic recovery (CRi; assessed in 218 patients) and overall survival (assessed in all 326 patients enrolled). Secondary endpoints included the duration of remission (DOR), minimal residual disease negativity (MRD-negative; <0.01% by central flow cytometry) in patients with CR/CRi, and stem cell transplantation (SCT) rate.
Preliminary results showed that InO performed better on most endpoints, with a significantly higher rate of CR/CRi than the SOC arm: 80.7 percent versus 33.3 percent (p<0.0001). The median duration of remission (DOR) was also longer in InO patients.
The safety profile of InO is consistent with previous studies, Dr. DeAngelo noted, with the most common grade ≥3 adverse event being cytopenias. Liver toxicities and veno-occlusive liver disease (VOD) were more common with InO than with SOC, with VOD occurring in 15 patients who received InO versus one who received SOC.
Patients received InO for a median of 8.3 weeks (range, 0.1-26.4 weeks), versus 0.9 weeks (range, 0.4-15.1 weeks) in the SOC arm. Eighty-three percent of patients in the InO arm discontinued treatment over the course of the study versus 89 percent in the chemotherapy arm, primarily due to CR (35% for INO; 40% for chemotherapy). More patients in the InO group eventually proceeded to allogenic SCT, compared with the SOC chemotherapy group, as well (48 and 20 patients, respectively).
The trial is ongoing to allow survival data to mature, and InO is being investigated in other early-phase clinical trials, including a phase I/II study of InO in elderly ALL patients and another phase I/II study of InO in patients with CD22-positive lymphoid malignancies.
DeAngelo D, Stelljes M, Martinelli G, et al. Efficacy and safety of inotuzumab ozogamicin (InO) vs standard of care (SOC) in salvage 1 or 2 patients with acute lymphoblastic leukemia (ALL): an ongoing global phase 3 study. Abstract #LB2073. Presented at the 2015 European Hematology Association, Vienna, Austria, June 14, 2015.