ALL-237 Bortezomib and Rituximab in De Novo Adolescent/Adult CD20-Positive, Ph-Negative Pre-B-Cell Acute Lymphoblastic Leukaemia: Updated 3-Year Results

Abstract

CD20 expression in B-cell precursor acute lymphoblastic leukemia (B-ALL) is associated with inferior outcomes. Treatment approaches involve the incorporation of rituximab (variable doses and scheduling between trials), intensification of chemotherapy, and allogeneic stem cell transplant in patients who continue to remain MRD- positive post-induction. Treatment intensification with chemotherapy or allogeneic stem cell transplantation for EOI MRD-positive patients is limited in resource constraint areas due to cost and infection-related morbidity and mortality. Hence, there is an unmet need to identify active and safe drugs to improve EOI MRD negative rates which can reduce the need for transplant and chemotherapy intensification. To test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged >14 years) with CD20 positive, Philadelphia-negative precursor B-ALL. Here we present updated results with longer follow up. Single-center, phase 2, nonrandomized open-label trial (Simon's two-stage design) conducted between December 2017 and August 2019. The primary endpoint of the study was the rate of (end of induction) EOI BM-MRD negativity. Secondary endpoints were EFS and OS. A total of 35 patients were enrolled between December 2017 and August 2019. EOI MRD negative rates were 70.1% compared with 51.7% in a historical cohort treated with chemotherapy. On longer follow up (median follow up 38months), 3-year EFS and OS rates were 75.6% (95% CI 62.3-91.9%), and 75.6% (95% CI 62.3-91.9%) respectively. 3-year rates of EFS based on post-induction (week 4) MRD status was 55.6% (31-99.7%) in MRD positive group compared with 86.1% (72.7-100%) in MRD negative group. 3-year rates of OS based on EOI MRD status was 55.6% (31-99.7%) in MRD positive group compared with 86.1% (72.7-100%) in MRD negative group. The median OS for patients who attained CR was not reached versus 8 months in patients who fail to achieve CR. On longer follow-up, the activity of the combination of bortezomib and rituximab is maintained without any new safety concerns. EOI MRD positivity and lack of complete remission post-induction are strong predictors of poor outcomes.