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% (<grade 3). After a median follow up of 18 months, event-free survival and overall survival were 81.8% and 84.7%, respectively.

Conclusion:

The combination of bortezomib, rituximab and paediatric-inspired ALL regimen is active and well tolerated in in de-novo CD20 positive Ph-negative precursor B-ALL.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.