Inotuzumab ozogamicin (InO) provides a bridge to cellular therapy in children and adolescents with CD22-positive relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), according to phase 2 results published in the Journal of Clinical Oncology.
The AALL1621 trial (ClinicalTrials.gov Identifier: NCT02981628) enrolled 48 patients with relapsed/refractory, CD22-positive B-ALL. Their median age was 9 (range, 1-21) years, and 60% were male. Most patients (67%) were in second or greater relapse at enrollment.
All patients received at least 1 dose of InO. The median number of cycles received was 2 (range, 1-6).
Response and MRD
After the first treatment cycle, 19 patients achieved a complete response (CR), and 9 had a CR with incomplete count recovery (CRi), for a CR/CRi rate of 58.3%.
The researchers evaluated minimal residual disease (MRD) in 27 of 28 patients with a CR/CRi. There were 18 patients (66.7%) with MRD less than 0.01%.
Of the 26 patients who received a second cycle of treatment, 13 had a CR/CRi and MRD less than 0.01%. In the entire study cohort, 30 patients (62.5%) achieved a CR or CRi within the first 2 cycles, and 21 (70%) had MRD less than 0.01% within 2 cycles.
The researchers identified CD22 modulation as a mechanism of resistance to InO. Partial CD22 expression and lower CD22 site density were linked to a reduced likelihood of response.
Survival and Safety
The median follow-up was 2.2 years. The estimated event-free survival (EFS) rate was 28.6% at 2 years and 19.6% at 3 years. The estimated overall survival (OS) rate was 36.0% at 2 years and 3 years.
Among patients who achieved MRD-negative CR/CRi within 2 cycles, the 2-year EFS rate was 57.7%, and the 2-year OS rate was 68.6%.
After InO treatment, 24 patients proceeded to hematopoietic stem cell transplant (HSCT) and 14 received chimeric antigen receptor (CAR) T-cell therapy. For patients who received HSCT (n=17) or CAR T-cell therapy (n=7) without bridging therapy, the 2-year EFS rate was 58.8% in the HSCT group and 68.6% in the CAR T-cell group.
The most common grade 3 or higher adverse events (AEs) in cycle 1 were febrile neutropenia (29.2%) and infection (16.7%). The most common grade 3 or higher AEs in cycle 2 were neutropenia (19.2%) and thrombocytopenia (19.2%). There were no InO-related deaths.
Sinusoidal obstruction syndrome (SOS) occurred in 12.5% of patients. All 6 had undergone HSCT. They all received defibrotide, 5 recovered, and 1 died from other HSCT complications.
“The study demonstrates the utility of InO as a bridge to HSCT or CAR T-cell therapy and highlights the need to identify modifiable sinusoidal obstruction syndrome risk factors for patients receiving HSCT after InO,” the researchers wrote.
Disclosures: This research was partially supported by Pfizer Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
O’Brien MM, Ji L, Shah NN, et al. Phase II trial of inotuzumab ozogamicin in children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia: Children’s Oncology Group Protocol AALL1621. J Clin Oncol. Published online January 10, 2022. doi:10.1200/JCO.21.01693