Survival benefits with bortezomib in children with T-cell lymphoblastic leukaemia

March 2022 Science Nalinee Pathak

The findings of the AALL 1231 trial have revealed survival benefits with bortezomib in children with  T-cell C (T-LL). Further, treatment with the proteasome inhibitor significantly lessened the need for cranial radiotherapy (CRT) in patients with T-cell acute lymphoblastic leukaemia (T-ALL). Findings of this clinical trial were recently published in the Journal of Clinical Oncology.

Study design

Between 2014 and 2017, the phase 3 AALL 1231 clinical study enrolled 824 patients with T-ALL or T-LL (stage II-IV) who were randomly (1:1)  divided to receive chemotherapy with or without bortezomib. Also, the investigators modified the treatment previously used in the phase 3 AALL0434 trial by replacing prednisone with the steroid dexamethasone and adding two extra doses of pegaspargase for eliminating CRT in most patients with T-ALL.

Result

The analysis of the AALL 1231 trial showed that the addition of bortezomib to chemotherapy significantly increased the 4-year event-free survival (EFS) to 86.4% ± 4.0% than those on chemotherapy alone (76.5% ± 5.1%, P = .041). Additionally, the 4-year overall survival (OS) was higher with bortezomib versus chemotherapy alone (89.5% ± 3.6% versus 78.3% ± 4.9%, P = .009). Notably, the number of patients (9.5%) with T-ALL scheduled to receive CRT was considerably reduced in this study compared to the AALL0434 clinical study (90.8%). However, there was no statistical difference in EFS (P = .412) and OS (P = .600) between patients who did not receive CRT in AALL1231 and patients who did receive CRT in the AALL0434 trial.

Conclusion

The study demonstrates the efficacy of bortezomib in providing significant clinical benefits to patients with T-ALL. Further, systemic therapy reduced CRT in more than 90% of T-ALL patients.

References

1. 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

2. CHOP-led study finds bortezomib improves survival in children with newly diagnosed T-cell lymphoblastic lymphoma. Children’s Hospital of Philadelphia. Published March 10, 2022. Accessed March 14, 2022. https://bit.ly/3w5ANuB

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