Bortezomib and Rituximab in Newly Diagnosed Adolescent and Adult CD20-Positive Philadelphia (Ph) Negative Precursor B-Cell Acute Lymphoblastic Leukemia: A Phase II Study

Background: The expression of CD20 in precursor B-cell ALL has been associated with poor outcomes. The addition of rituximab with intensive chemotherapy in this subset of ALL has led to improvement in the event-free survival. Further increment in outcomes require novel approaches. Bortezomib is an active drug in relapsed ALL as well as has synergistic activity with rituximab in B-cell lymphomas; thus the addition of bortezomib to rituximab and chemotherapy may improve the outcomes in CD20-positive precursor B-cell ALL. Methods: We conducted a phase II study to test the activity of bortezomib and rituximab in combination with a paediatric inspired regimen during induction therapy in newly diagnosed adolescent and adults (>14 years of age) with CD20-positive, Philadelphia (Ph)-negative precursor B-ALL, with bone marrow measurable residual disease (MRD) negativity at the end of induction (EOI) as the primary endpoint. Results: From December 2017 through August 2019, a total of 35 patients were enrolled. A total of 70.99% patients achieved EOI MRD negative status. MRD negative rates improved to 88% post consolidation. There was no significant increase in toxicity with addition of bortezomib and rituximab to standard chemotherapy. The incidence of neuropathy was 26% (