Philadelphia, March 10, 2022—Adding the proteasome inhibitor bortezomib to chemotherapy significantly improved the overall survival of children and young adults with newly diagnosed T-cell lymphoblastic lymphoma (T-LL), according to a Children’s Oncology study Group (COG) conducted by researchers at Children’s Hospital of Philadelphia (HACHER). This international phase 3 clinical trial 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 findings were published in the Journal of Clinical Oncology.

“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,” said study chair and first author David T. Teachey. , MD, 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 therapy for cure and also suggest that bortezomib should be considered part of the new standard of care for patients newly diagnosed with lymphoma. T-cell lymphoblastic.”

With advances in treatment, the overall survival of children with T-ALL and T-LL is approaching that of B-cell acute lymphoblastic leukemia (B-ALL) and B-cell lymphoblastic lymphoma (B-LL), with a 5-year survival rate of about 85%. However, less than 35% of patients with T-ALL and relapsed T-LL survive. To improve outcomes in these patients, COG trials have focused on different strategies to prevent relapse in newly diagnosed patients, including refining risk stratification, introducing new drugs and treatments, and intensifying chemotherapy.

While results were excellent in the Phase 3 clinical trial of COG AALL0434, the majority of children with T-ALL received cranial radiation therapy (CRT), which can have significant long-term side effects, including secondary cancers, brain tumors and neurocognitive decline which can significantly affect academic performance and employability.

Therefore, in the AALL1231 trial (NCT02112916), researchers further modified the treatment, using the steroid dexamethasone instead of prednisone during chemotherapy and adding two additional doses of pegaspargase with the aim of eliminating CRT in most patients with T-ALL. Of the 824 patients enrolled in the trial between 2014 and 2017, half also received bortezomib, a proteosome inhibitor, based on strong preclinical evidence for its use in relapsed T-LL and T-ALL.

For patients with T-LL, 4-year event-free survival and overall survival were significantly improved for patients on bortezomib plus chemotherapy compared to chemotherapy alone: ​​86.4% and 89.5% versus 76, 5% and 78.3%, respectively. The researchers also did not observe excessive toxicity with bortezomib.

“This is the first trial demonstrating an overall survival benefit for newly diagnosed pediatric T-LL with a small molecule inhibitor,” said study senior author Stephen P. Hunger, MD, chief of the Division of Oncology, Director of the Center for Childhood Cancer Researcher and Jeffrey E. Perelman Distinguished Professor of the Department of Pediatrics at Children’s Hospital of Philadelphia. “Before this study, the only drugs that improved the survival of newly diagnosed T-ALL/T-LL patients were cytotoxic chemotherapies. The success of bortezomib in this trial could potentially change the approach to first-line treatment of T-LL. »

Although the overall outcomes in patients with T-ALL were not statistically significantly improved by bortezomib, researchers were able to eliminate CRT in almost all patients with T-ALL on bortezomib while still achieving excellent results for most patients. Indeed, while 90.8% of T-ALL patients in the previous trial received CRT, less than 10% received it in this trial, and yet patients who did not receive CRT did not receive CRT. had no statistical difference in the results.

The COG trial involved 212 sites around the world. The study was funded by the National Cancer Institute, part of the National Institutes of Health (R01CA193776, U10CA180886, U24CA196173, U10CA180899, X01HD100702, R03CA256550, R01CA264837), the Leukemia and Lymphoma Society, the St. Baldrick’s Foundation, and the American Associated charities. The study was supported by Millennium Pharmaceuticals, Inc. through a cooperative research and development agreement with the NCI.

Teachey et al. “Children’s Oncology Group Trial AALL1231: A Phase 3 Clinical Trial Testing Bortezomib in Newly Diagnosed T-cell Acute Lymphoblast Leukemia and Lymphoma” Journal of Clinical OncologyMarch 10, 2022, DOI: 10.1200/JCO.21.02678

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About Children’s Hospital of Philadelphia: A non-profit charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and launching important research initiatives, the 595-bed hospital has fostered many discoveries that have benefited to children all over the world. Its pediatric research program is one of the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty and surgical care centers, emergency and community hospital alliances across Pennsylvania and New Jersey. , as well as a new inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have earned The Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

About the Children’s Oncology Group (COG)

COG (childrensoncologygroup.org), a member of the NCI National Clinical Trials Network (NCTN), is the world’s largest organization devoted exclusively to childhood and adolescent cancer research. COG brings together more than 10,000 childhood cancer experts from more than 200 leading hospitals, universities and children’s cancer centers in North America, Australia and New Zealand in the fight against childhood cancer. Today, more than 90% of the 17,000 children and adolescents diagnosed each year with cancer in the United States are cared for at COG member institutions. Research conducted by COG institutions over the past 50 years has transformed childhood cancer from a virtually incurable disease to one with an 80% combined 5-year survival rate. COG’s mission is to improve cure rates and outcomes for all children with cancer.


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