Adding bortezomib to chemotherapy improves survival outcomes for children and young adults with previously untreated T-cell lymphoblastic lymphoma (T-LL), according to phase 3 results published in the Journal of Clinical Oncology.

The addition of bortezomib to modified augmented Berlin-Frankfurt-Munster (aBFM) chemotherapy significantly improved 4-year event-free survival (EFS) and overall survival (OS) for T-LL patients in this trial.

The COG AALL1231 trial (ClinicalTrials.gov Identifier: NCT0211291) was designed to investigate the efficacy of bortezomib plus modified aBFM in patients with T-LL and T-cell acute lymphoblastic leukemia (T-ALL) who were 1 to 30 years of age.


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A secondary goal of the trial was to reduce the use of prophylactic cranial radiotherapy (CRT) in patients with standard- or intermediate-risk T-ALL. Several changes were made to the aBFM backbone used in the predecessor AALL0434 trial (ClinicalTrials.gov Identifier: NCT00408005) to enhance central nervous system-directed therapy and limit CRT.

The study included 824 evaluable patients — 615 with T-ALL and 209 with T-LL. The patients were randomly assigned to receive a modified aBFM backbone with bortezomib (n=408) or without it (n=416) during induction and delayed intensification.

In the overall study population, there was no improvement in 4-year EFS or OS with bortezomib. The EFS rate was 83.8% in the bortezomib arm and 80.1% in the control arm (hazard ratio [HR], 0.833; P =.131). The OS rates were 88.3% and 85.7%, respectively (HR, 0.772; P =.085).

However, among patients with T-LL, bortezomib significantly improved EFS and OS. The 4-year EFS rate was 86.4% in the bortezomib arm and 76.5% in the control arm (HR, 0.563; P =.041). The 4-year OS rate was 89.5% and 78.3%, respectively (HR, 0.421; P =.009).

In all, 9.5% of patients were scheduled to receive CRT. A direct comparison between patients in the predecessor AALL0434 trial who received CRT with similar patients in the current AALL1231 trial who did not receive CRT demonstrated similar EFS (P =.412) and OS (P =.600).

The incidence of grade 3 or higher toxicity was similar between the bortezomib arm and the control arm (80.0% and 76.5%, respectively; P =.234).

Grade 4 or higher pulmonary toxicity during induction and delayed intensification occurred in 15 patients in the bortezomib arm and 11 patients in the control arm (P =.393). The overall rate of peripheral neuropathy was similar between the arms.

“Incorporating bortezomib into standard therapy for de novo T-LL appears advantageous,” the researchers concluded. “With modern chemotherapy regimens, more than 80% of children and young adults with T-ALL can be cured without CRT.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Teachey DT, Devidas M, Wood BL, et al. Children’s Oncology Group Trial AALL1231: A phase III clinical trial testing bortezomib in newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma. J Clin Oncol. Published online March 10, 2022. doi:10.1200/JCO.21.02678