Bortezomib Improves Survival in Children With Newly Diagnosed T-LL, Study Results Show

Analysis of the trial show that intensifying the chemotherapy regimen allowed for elimination of radiation in 90% of pediatric patients with T-cell acute lymphoblastic leukemia.

Adding the proteasome inhibitor bortezomib to chemotherapy significantly improved overall survival in children and young adults with newly diagnosed T-cell lymphoblastic lymphoma (T-LL), according to the results of a study conducted by the Children’s Oncology Group (COG).

The phase 3 clinical trial, led by investigators at the Children’s Hospital of Philadelphia (CHOP), 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.

“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,” David Teachey, MD, director of Clinical Research at the Center for Childhood Cancer Research at CHOP, said in a statement. “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-cell lymphoblastic lymphoma.”

With treatment advancements, the overall survival (OS) for children with T-ALL and T-LL approximates that of B-cell acute lymphoblastic leukemia and B-cell lymphoblastic lymphoma, with a 5-year survival rate of approximately 85%, according to investigators.

However, less than 35% of individuals with relapsed T-ALL and T-LL survive. The COG trials aim to focus on different strategies to prevent relapse in newly diagnosed individuals. The strategies include introducing new drugs and treatments, intensifying chemotherapy, and refining risk stratification.

The outcomes of the COG phase 3 clinical trial AALL0434 showed that a majority of children with T-ALL received cranial radiotherapy (CRT), which can cause long-term adverse events, including brain tumors, neurocognitive decline, and second cancers.

Investigators modified the treatment further during the trial by using the steroid dexamethasone instead of prednisone during chemotherapy and adding 2 extra doses of pegaspargase, with a goal of eliminating CRT in most individuals with T-ALL.

Of the 824 individuals enrolled in the trial between 2014 and 2017, about half also received proteosome inhibitor bortezomib, which was based on string preclinical data for its use in relapsed T-ALL and T-LL.

Investigators found that, for individuals with T-LL, the 4-year event-free survival and OS improved significantly for those on bortezomib plus chemotherapy compared with chemotherapy alone, at 86.4% and 89.5% in the bortezomib group compared with 76.5% and 78.3% in the chemotherapy group, respectively.

They did not observe any excess toxicity with bortezomib.

“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,” Stephen Hunger, MD, chief of the Division of Oncology and director of the Center for Childhood Cancer Research, said in the statement.

Although the overall outcomes in individuals with T-ALL did not statistically significantly improve with bortezomib, the investigators were able to eliminate CRT in almost all individuals with T-ALL on bortezomib and still achieve excellent outcomes for most individuals.

About 90.8% of individuals with T-ALL in the earlier trial received CRT, while less than 10% of those in the new trial received it. However, those who did not receive CRT had no statistical differences in outcomes.

Reference

CHOP-led study finds bortezomib improves survival in children with newly diagnosed T-cell lymphoblastic lymphoma. EurekAlert. News release. March 10, 2022. Accessed March 15, 2022. https://www.eurekalert.org/news-releases/945735.