The researchers of the Children’s Hospital of Philadelphia (CHOP) revealed in a study supported by the Children’s Oncology Group (COG) than to enhance the chemotherapy with the addition of the proteasome inhibitor bortezomib significantly improved overall survival in children and young adults with newly diagnosed T-cell lymphoblastic lymphoma (T-LL).
It’s about a Phase 3 international research which also revealed that radiation can be eliminated in 90% of children with acute lymphoblastic leukemia T-cell (T-ALL) when the chemotherapy regimen is intensified.
THE results of the study were published in the scientific journal Journal of Clinical Oncology.
Bortezomib: this is how it works
“The results of this study have the potential to change the standard of care for patients with T-cell lymphoblastic lymphoma and acute T-cell lymphoblastic leukemia.Said the study’s president and first author David T. Teachey, attending physician and director of clinical research at the Center for Childhood Cancer Research at Children’s Hospital of Philadelphia.
“The data show that most patients with T-ALL no longer require cranial radiation for care and also suggest that bortezomib should be considered as part of the new standard of care for newly diagnosed patients with T-cell lymphoblastic lymphoma.“, Teachey continued.
With advances in therapies, overall survival for children with T-ALL and T-LL approaches that of B-cell acute lymphoblastic leukemia (B-ALL) and B-cell lymphoblastic lymphoma (B-LL), with a 5-year survival rate of approximately 85%. However, less than 35% of patients with relapsed T-ALL and T-LL survive.
To improve survival in patients, COG studies have focused on several strategies to prevent relapse in newly diagnosed patients, including refining risk stratification, the introduction of new drugs and treatments and the intensification of chemotherapy.
Results were excellent in the previous Phase 3 COG AALL0434 clinical trial, most children with T-ALL received cranial radiation therapy (CRT), which can have significant long-term side effects, including second tumors, brain tumors, and neurocognitive decline that can significantly affect academic achievement and employability.
In study AALL1231 (NCT02112916), researchers further modified therapies, taking advantage of the steroid dexamethasone instead of prednisone during chemotherapy and adding two extra doses of pegaspargase with the goal of eliminating CRT in most patients with T-ALL.
Of the 824 patients enrolled in the study between 2014 and 2017, half also received bortezomib, a proteasome inhibitor, based on strong preclinical data for its use in T-LL and T-ALL relapse.
For patients with T-LL, both 4-year relapse-free survival and overall survival were significantly improved for patients treated with bortezomib plus chemotherapy compared to chemotherapy alone: 86.4% and 89.5% versus 76, 5% and 78.3%, respectively. The researchers also specified that no excessive toxicity was found with bortezomib.
“This is the first study demonstrating an overall survival benefit for newly diagnosed pediatric T-LL with a small molecule inhibitorSaid the senior author of the study Stephen P. Hunger, MD, head of the division of oncology, director of the Center for Childhood Cancer Researcher and holder of the Jeffrey E. Perelman Distinguished Chair at Department of Pediatrics of the Children’s Hospital of Philadelphia.
“Prior to this study, the only drugs that improved survival for newly diagnosed T-ALL / T-LL patients were cytotoxic chemotherapy drugs. The success of bortezomib in this study could potentially change the approach to the frontline treatment of T-LL “Hunger explained.
Although overall outcomes in T-ALL patients were not statistically significantly improved by bortezomib, investigators were able to eliminate CRT in nearly all T-ALL patients receiving bortezomib and still achieve excellent results for the majority of patients with T-ALL. part of the patients. Indeed, while 90.8% of patients with T-ALL in the previous study received CRT, less than 10% received it in this study, yet patients who did not receive CRT had no statistical difference in outcomes.
The COG process involved 212 sites around the world.
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