Targeted Therapy for Children with High-Risk Hodgkin Lymphoma (HL) Proven in Large Multicenter Clinical Trial Conducted by Children’s Oncology Group (COG) Can significantly reduce recurrence rates and lead to completion by pediatric oncologists at Roswell Park Comprehensive Cancer Center, Children’s Healthcare of Atlanta, and Emory University’s Winship Cancer Institute. By combining the targeted antibody drug conjugate (ADC) brentuximab vedotin (BV) with standard chemotherapy regimens, children were 10% less likely to relapse. The findings were published today in the New England Journal of Medicine ( New England Journal of Medicine). “We saw a 10% improvement in event-free survival—a real breakthrough,” said senior researcher Author Kara Kelly, MD, chair of the Roswell Park Oishei Children’s Cancer and Blood Disorders Program and director of the Division of Pediatric Hematology/Oncology at the Jacobs School of Medicine and School of Biomedical Sciences at the University at Buffalo. “This is a big win, especially in this field. We anticipate that this treatment option will soon become the standard of care for children with high-risk Hodgkin’s lymphoma.” Clinical trial AHOD1331 (NCT02166463) was funded by the National Cancer Institute (NCI) of the National Institutes of Health at 153 COG sites. The research was also supported by Seagen (formerly Seattle Genetics) and the St. Baldrick Foundation. The study was sponsored by the NCI Division of Cancer Therapy and Diagnostics, and brentuximab vedotin was provided by Seagen under a collaborative development agreement with NCI.
” The trial reflects a paradigm shift in advanced Hodgkin lymphoma in children, introducing the first A Targeted Approach to Initial Treatment of Hodgkin’s Lymphoma and the First New Regimen in Two Decades,” study first author Sharon Castellino, MD, MS, Leukemia and Lymphoma Program, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta Director, Professor of Pediatrics at Emory University School of Medicine and Investigator at the Winship Cancer Institute said Emory University Research Institute. Dr. Castellino succeeds Dr. Kelly this year as Chair of the COG Hodgkin Committee. “We are optimistic that this trial will set the stage for FDA approval of this targeted antibody-drug conjugate for children and adolescents.”
study vice chair and co-author Frank Keller, MD, Pediatric Hematologist/Oncologist, Aflac Cancer and Blood Disorders Center, Atlanta, and Professor of Pediatrics, Emory University School of Medicine, added: ” Demonstrating the effectiveness of a highly targeted therapy against a malignant cell population in newly diagnosed high-risk Hodgkin lymphoma pediatric and young adult patients is an important step toward improving cure rates and may not add significantly to this young population Many years of life left with long-term toxicity.” HL is a patient aged 12-29 most common cancer. Despite its high five-year survival rate—97% of people under 19 are alive five years after diagnosis—about a third of survivors are classified as high risk; of these, about 15-20 % will recur.
COG study – largest and only randomized phase 3 trial ever conducted in newly diagnosed pediatric patients with high-risk HL Targeting ADCs via CD-30 – Involved 587 patients aged 2-21 with previously untreated disease.
Patients were randomly assigned to one of two groups, each receiving over five 21-day cycle of treatment. The control group received standard pediatric chemotherapy regimens.
The second group received the standard pediatric chemotherapy regimen plus brentuximab vedotin. Brentuximab vedotin (BV) is an antibody-drug conjugate that specifically targets the CD30 protein on the surface of HL cancer cells, destroying them while sparing mostly healthy cells.
Both groups received local radiotherapy based on response assessed after two treatment cycles. About three and a half years after treatment, the event-free survival rate in the brentuximab vedotin group was 92.1 % compared with 82.5% in the control group – an overall reduction in the risk of recurrence, death, or second malignancy of 59%.
The lower risk of relapse may eliminate the need for retreatment with additional toxic therapies. In the long run, treatment toxicity puts HL survivors at very high risk for breast cancer, stroke, myocardial infarction, restrictive lung disease, infertility, and shortened lifespan.
“Brentuximab vedotin is not expected to produce long-term toxicity,” Dr. Kelly said, noting that in the treatment phase of the clinical trial , less than 10% of patients who received it required dose reductions. “Because the drug could be administered more consistently, its efficacy improved without an increase in neuropathy or serious infection.”
Dr. Kelly, Dr. Castellino and colleagues, with support from the National Cancer Institute, will build on these findings in a new clinical trial that will begin in early 2023. The Phase III randomized study will enroll approximately 1,900 children and adults aged 5-60 with low-to-intermediate risk HL. Objective: To determine whether the combination of the CD30-targeting ADC brentuximab vedotin and the immunotherapeutic nivolumab can prolong progression-free survival and further reduce the time patients spend on standard chemotherapy and radiation. Patients will be followed for 12 years to monitor their progress and assess outcomes.
Allison Brashear, MD, Vice President Dean of the University at Buffalo School of Health Sciences and Jacobs Medicine The study’s findings “mean a vastly improved quality of life for the most vulnerable and bravest children with cancer,” said the dean of the Faculty of Biomedical Sciences. “As one of the greatest demonstrations of the success of the immuno-oncology approach to children with cancer,” Dr. Brashear noted, “it is a powerful example of when extraordinary institutions decide to collaborate What happens when is the key to their success. “
Lucky Jain, MD, MBA, Chief Pediatrician, Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine Head of the department, he said: “A 10% reduction in the recurrence rate in children with high-risk Hodgkin’s lymphoma is an important milestone for the field of medical cancer. Children’s Healthcare of Atlanta and Emory University are proud of this incredible leap led by our physicians, Dr. Sharon Castellino and Dr. Frank Keller, along with their collaborators and the Children’s Oncology Group. ”
More information:
Sharon M . Castellino et al, Brentuximab Vedotin Combined with Chemotherapy in Pediatric High-Risk Hodgkin Lymphoma, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2206660
Citation
: Pediatric Multicenter Study Shows Targeted Therapy for High-Risk Hodgkin’s Lymphoma Reduces Relapse (2022, November 3), Retrieved November 17, 2022 from https://medicalxpress.com/news /2022-11-pediatric-multicenter-therapy-high-risk-hodgkin.html
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