In a phase II trial (Children’s Oncology Group AALL1621) reported in the Journal of Clinical Oncology, O’Brien et al found that inotuzumab ozogamicin produced a high response rate in children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Study Details
In the U.S. multicenter trial, 48 patients aged 1 to 21 years were enrolled between June 2017 and May 2019. Patients received inotuzumab ozogamicin at 0.8 mg/m2 on day 1 and at 0.5 mg/m2 on days 8 and 15 of a 28-day cycle, with response evaluated at day 28.
The primary endpoint was the rate of complete response or complete response with incomplete count recovery after cycle 1.
Responses
After cycle 1, 19 patients had a complete response and 9 had a complete response with incomplete count recovery (response rate = 58.3%, 90% confidence interval = 46.5%–69.3%). Evaluation in 27 patients with complete response/complete response with incomplete count recovery showed measurable residual disease (MRD) at < 0.01% in 18 (66.7%) and MRD at 0.01% to 0.099% in 3 (11.1%). Delayed count recovery past day 42 was observed in 7 (25%) of the 28 patients with complete response/complete response with incomplete count recovery after cycle 1.
Among 27 patients with paired pre– and post–cycle 1 samples, median baseline CD22 antibody bound per cell was 1,022 sites/cell among 13 nonresponders vs 4,123 sites/cell among 14 responders (P = .008). Median baseline CD22% was similar but had a wider range among nonresponders (98%, range = 40%–100%) vs responders (99%, range = 92.9%–100%; P = .014).
Among nonresponders, antibody bound per cell did not change significantly pre– and post–cycle 1, but CD22% decreased in 8 of 13 (median = 82%, range = 1.4%–100%) vs baseline (P = .007). Among the four patients with baseline CD22% < 90%, evaluation after cycle 1 showed the emergence of predominantly CD22-negative populations.
Adverse Events
The most common adverse events of any grade in cycle 1 were febrile neutropenia (29.2%) and infection (16.7%). Grade 3 alanine transaminase elevation was observed in three patients (6.3%), and grade 3 hyperbilirubinemia occurred in 1 patient. Aspartate transaminase elevation of any grade was observed in five patients (10.4%). Among 21 patients undergoing hematopoietic stem cell transplantation after treatment with inotuzumab ozogamicin, 6 (28.6%) developed grade 3 sinusoidal obstruction syndrome. No treatment-related deaths occurred.
The investigators concluded, “[Inotuzumab ozogamicin] is effective and well tolerated in heavily pretreated children and adolescents with [relapsed/refractory] CD22-positive B-cell ALL. Sinusoidal obstruction syndrome after hematopoietic stem cell transplantation and prolonged cytopenias were notable. CD22 modulation was identified as a mechanism of resistance. Expanded study of inotuzumab ozogamicin combined with chemotherapy is underway.”
Maureen M. O’Brien, MD, MS, of the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute, St. Baldrick’s Foundation, and Pfizer Inc. For full disclosures of the study authors, visit ascopubs.org.
