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Does Bortezomib Improve Survival in Children With T-cell Lymphoblastic Leukemia?

Published on April 4, 2022 in Cornerstone Blog · Last updated 5 months 3 weeks ago


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CHOP researchers found that bortezomib improved survival in T-LL.

The findings

Adding bortezomib, a proteasome inhibitor, to chemotherapy significantly improved overall survival in children and young adults with newly diagnosed T-cell lymphoblastic lymphoma (T-LL). The researchers also found that radiation could be eliminated in 90% of children with T-cell acute lymphoblastic leukemia (T-ALL) when the chemotherapy regimen was intensified.

Why it matters

Outcomes in patients with relapsed T-ALL/T-LL remain poor, so Children's Oncology Group (COG) trials have focused on preventing relapse in patients with newly diagnosed T-ALL/T-LL. In previous studies, bortezomib demonstrated encouraging safety and efficacy in relapsed T-ALL/T-LL. In addition, most patients with T-ALL receive cranial radiotherapy, which is associated with significant long-term morbidity.

Who conducted the study

Matthew Weitzman, PhD

David T. Teachey, MD

David T. Teachey, MD, attending physician and director of Clinical Research at the Center for Childhood Cancer Research at Children's Hospital of Philadelphia, was the study chair and first author of the Children's Oncology group study. Stephen P. Hunger, MD, chief of the Division of Oncology, and director of the Center for Childhood Cancer Research, was the senior study author.

How they did it

In this phase-3, COG-initiated, international randomized clinical trial, 824 children and young adults with T-ALL/T-LL were randomly assigned to a modified, augmented Berlin-Frankfurt Münster (aBFM) chemotherapy regimen with or without bortezomib. Modifications were made to this treatment, including using dexamethasone instead of prednisone, and adding extra doses of pegaspargase – one of the chemotherapy agents – in hopes of eliminating the need for cranial radiotherapy for most patients.

Leukemia Cell Photo

Researchers also found that they could possibly eliminate the need for radiotherapy in T-ALL.

In patients with T-LL, the event-free survival at four years was significantly higher in the bortezomib art (86.4% vs. 76.5%), as was the overall survival (89.5% vs. 78.3%). Although bortezomib did not confer a survival benefit in patients with T-ALL, significantly fewer patients (9.5%) required cranial radiotherapy compared with previous trials. Bortezomib also did not lead to any excess toxicity.

Quick thoughts

"The results of this trial have the potential to change the standard of care for patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukemia," Dr. Teachey said. "The data show that most patients with T-ALL no longer need cranial radiation for cure and also suggest bortezomib should be considered as part of the new standard of care for newly diagnosed patients with T-LL."

Dr. Hunger added: "This is the first trial demonstrating an overall survival benefit for newly diagnosed pediatric T-LL with a small molecule inhibitor. Before this study, the only drugs that have improved survival for newly diagnosed T-ALL/T-LL patients have been cytotoxic chemotherapeutics. The success of bortezomib in this trial could potentially change the approach to frontline treatment of T-LL."

Where the study was published

The study appeared in the Journal of Clinical Oncology.

Want to learn more?

Find out more in the CHOP press release.