Bortezomib-based Anthracycline-free Induction for Pediatric Relapsed ALL as a Bridge to Immunotherapy

Background: Immunotherapy may lead to durable remissions in patients with relapsed and refractory acute lymphoblastic leukemia (R/R ALL). Patients receiving immunotherapy with a lower disease burden tend to have improved long-Term outcomes and less toxicity. Thus, an induction protocol to achieve lower disease burden is required. Bortezomib added to a 4-drug induction was shown to lead to high rates of remission in R/R ALL patients. Inclusion of anthracyclines in this protocol may preclude most patients, having maximized the cumulative dose of anthracyclines. Thus, our goal was to evaluate anthracycline-free bortezomib-based induction for patients with R/R ALL. Procedure: We conducted a retrospective analysis of patients treated with bortezomib-based protocols for R/R ALL between 2011 and 2019 at our center. Data regarding toxicity and response rate was collected and analyzed. Results: Eighteen children with R/R ALL were treated with bortezomib-based induction, 13 of them without anthracyclines. Eleven patients did not complete the induction course: 6 due to toxicity, and 5 due to physician decision to proceed to immunotherapy early. Two events of treatment-related mortality occurred. There was no significant difference in toxicity between patients who treated with anthracycline and those who were not. Ten patients achieved complete remission, with 4 patients having polymerase-chain-reaction minimal residual disease below 10^-4. Fifteen patients proceeded directly to immunotherapy: 11 patients received CD19 chimeric-Antigen receptor-T-cells, 2 blinatumomab and 2 hematopoietic stem cell transplant. Conclusion: Anthracyclines can be safely omitted from bortezomib-based therapies in patients with R/R ALL, when planning to proceed to immunotherapy.