Treatment with inotuzumab ozogamicin was found to be safe and effective in a phase III study for patients with relapsed or refractory acute lymphoblastic leukemia.
Mark Shapiro, MD
Treatment with inotuzumab ozogamicin was found to be safe and effective in a phase III study for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) that was presented at the 20th Congress of the European Hematology Association (EHA). Overall survival (OS) data were not yet mature at the time of the analysis.
"Mature overall survival data is dependent on the accrual of additional events," Mark Shapiro, MD, Global Medical Affairs Lead, Hematology Programs at Pfizer, the developer of the drug, said regarding the findings. "We are currently in discussions with regulatory authorities to determine how to bring this important new therapy to patients as soon as possible."
Inotuzumab ozogamicin is an antibody-drug conjugate that consists of the monoclonal antibody inotuzumab, which targets the CD22 cell surface antigen, linked to a cytotoxic agent. CD22 is expressed on approximately 90% of B-cell malignancies.
In the open-label phase III study, 326 patients were enrolled, with the first 218 selected for the primary analysis. One hundred and nine patients received inotuzumab ozogamicin at a starting dose of 1.8 mg/m2 each cycle, which consisted of a 0.8 mg/m2 dose on day 1 followed by 0.5 mg/m2 on day 8 and day 15. In the chemotherapy arm, 109 patients received physicians’ choice of fludarabine plus cytarabine with G-CSF, high-dose cytarabine, or cytarabine plus mitoxantrone.
The dual primary endpoint was complete response (CR) or CR with incomplete platelet recovery (CRi) and OS. Secondary endpoints included duration of remission (DOR), minimal residual disease (MRD)-negativity (<0.01% cells by central flow cytometry) in those with CR/CRi, and stem cell transplantation (SCT) rate.
The CR/CRi rate with inotuzumab ozogamicin was 80.7% compared with 33.3% in those treated with chemotherapy, representing more than a doubling in response with inotuzumab ozogamicin (P<.0001). In complete responders, MRD-negativity was achieved in 78.4% versus 28.1%, with inotuzumab ozogamicin and chemotherapy, respectively (P<.0001).
The duration of first complete remission was ≥12 months in 43% of patients treated with inotuzumab ozogamicin compared with 35% in the chemotherapy arm. The median DOR was 4.6 months with inotuzumab ozogamicin compared with 3.1 months for chemotherapy (P= .0169).
Side effects were assessed in 259 patients from the full study population. This analysis consisted of those who received ≥1 dose of inotuzumab ozogamicin (n = 139) or chemotherapy (n = 120). The median duration of treatment in the inotuzumab ozogamicin arm was 8.3 weeks versus 0.9 weeks with chemotherapy.
Eighty-three percent of patients in the inotuzumab ozogamicin arm discontinued treatment over the course of the study versus 89% in the chemotherapy arm. The most common cause of discontinuation in the inotuzumab ozogamicin arm was CR (35%) compared with resistant disease in the chemotherapy arm (40%). The number of patients receiving SCT was doubled in the inotuzumab ozogamicin arm (n = 48) compared with chemotherapy (n = 20).
The most frequently observed grade ≥3 adverse events (AEs) in both arms were hematologic cytopenias. Grade ≥3 hepatobiliary AEs were seen in 9% of patients treated with inotuzumab ozogamicin versus 3% with chemotherapy. All grade veno-occlusive liver disease (VOD) occurred in 15 patients (13 were grade ≥3) in the inotuzumab ozogamicin arm versus 1 in the chemotherapy arm. The majority of VOD cases were seen after SCT (n = 10). In total, there were 2 deaths associated with VOD in the inotuzumab ozogamicin arm.
Analysis of the phase III study remains ongoing. Based on the initial assessment of the trial, Pfizer, the company developing the drug, has entered into discussions with the FDA and other regulatory authorities.
DeAngelo DJ, 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. Presented at: 20th Congress of the European Hematology Association (EHA); Sunday, June 14, 2015; Vienna, Austria. Abstract #LB2073.