Investigational treatment options in phase I and phase II trials for relapsed or refractory acute lymphoblastic leukemia in pediatric patients

Antibody and Cellular-Based Therapies for Pediatric Acute Lymphoblastic Leukemia: Mechanisms and Prospects

“…CD38 is a cell surface protein that is overexpressed in T lymphocytes and low in normal cells. Daratumumab (an anti-CD38 antibody) is currently being studied for the treatment of T-cell ALL, showing complete remissions in 5 out of 8 patients [7].…”

“…Denintuzumab mafodotin, an anti-CD19 antibody conjugated with dolastatin 10, was used in a phase 1 study to treat adult patients with refractory or relapsed B-cell ALL, and the complete response rate was only 20%. Although it passed the pediatric preclinical testing program, the drug has a low priority in the pediatric B-cell ALL population [7]. Further, dual-targeted ADC drugs that target CD19 and CD20, combotox, exhibited a complete remission rate of 17.6% against pediatric ALL [25].…”

“…In a Phase 1/2 trial of 70 children with relapsed or refractory B-cell ALL at the recommended dose of blinatumomab, 39% of the subjects achieved complete remission within the first 2 cycles, of which 52% were MRD negative [30]. The children’s oncology group completed a phase 3 trial in children with first relapses of B-cell ALL, and patients treated with blinatumomab had significantly better 2-year disease-free survival compared with patients randomized to chemotherapy (59% vs. 41%) [7]. In addition, blinatumomab in maintenance therapy seems promising to reduce chemotherapy and shorten treatment time.…”

“…Recently, a novel CD22 CAR-T-cell therapy with promising preclinical efficacy was developed for pediatrics B-cell ALL [35]. Since many potential target antigens are present in normal and malignant T-cell, some CAR-T therapies (such as anti-CD5 and anti-CD7 CAR-T cells) for T-cell ALL are still in the early stages of clinical development [7]. Furthermore, allogenic CAR-T cells are also known as “off-the-shelf CARs,” and endogenous T-cell receptors are often removed to prevent graft-versus-host disease and rejection.…”

“…In addition, 10% of patients with classical multidrug chemotherapy had an initial refractory disease. Many patients also face subsequent relapses; the survival rate of patients with relapsed B-cell ALL is about 50%, and that of patients with relapsed T-cell All is only about 20% [7]. Hence, new treatment methods, such as immunotherapy, have been developed to improve the prognosis of ALL further and reduce adverse reactions.…”