Brentuximab Vedotin Found to Lower Relapse Rate in Pediatric Patients With High-Risk Hodgkin Lymphoma

Study shows combining brentuximab vedotin with the standard chemotherapy regimen reduced the risk of relapse in children with high-risk Hodgkin lymphoma by 10%.

Administration of a targeted therapy for children with high-risk Hodgkin lymphoma (HL) was found to significantly decrease relapse rates in a large multicenter clinical trial conducted by the Children’s Oncology Group (COG) and published in The New England Journal of Medicine.

The clinical trial, AHOD1331 (NCT02166463), was conducted at 153 COG sites. The results showed that combining brentuximab vedotin (BV) with the standard chemotherapy regimen reduced the risk of relapse in children with HL by 10%. BV is an antibody-drug conjugate (ADC) that targets the CD30 protein on the surface of HL cancer cells, thereby eliminating them while mostly avoiding damage to healthy cells.

“We saw a 10% improvement in event-free survival—a real breakthrough,” study senior author Kara Kelly, MD, chair of the Roswell Park Oishei Children’s Cancer and Blood Disorders Program, and division chief of Hematology/Oncology in the Department of Pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, said in a press release. “That’s quite a big gain, especially in this field. We expect that this treatment regimen will soon become standard of care for pediatric patients with high-risk Hodgkin lymphoma.”

Among patients diagnosed with HL, 97% less than 19 years of age are alive 5 years after diagnosis. Approximately one-third of survivors are classified as high risk, of whom approximately 15%-20% will relapse.

The phase 3 AHOD1331 trial enrolled 587 high-risk pediatric patients with HL between 2 and 21 years of age with previously untreated disease. The patients were randomized to 1 of 2 arms, with both arms receiving treatment over five 21-day cycles. Those in the control group were administered the standard pediatric chemotherapy regimen, whereas the second group received the standard pediatric chemotherapy regimen, plus BV.

Both groups received site radiation therapy based on responses assessed following 2 cycles of treatment. A follow-up conducted approximately 3 and a half years post treatment found a 92.1% event-free survival rate in the BV cohort vs 82.5% in the control cohort. This represents an overall risk reduction of 59% for relapse, death, or a second malignant neoplasm.

The reduced risk of relapse may eliminate the need for re-treatment with additional toxic therapies. The researchers noted that the toxicity from long-term treatment with these toxic medications puts HL survivors at a very high risk of breast cancer, myocardial infarction, restrictive pulmonary disease, infertility, and shortened lifespan.

“Brentuximab vedotin is not anticipated to have long-term toxicity,” Kelly said in a press release. “Because the drug could be given more consistently, its efficacy improved with no increase in neuropathy or serious infection.”

These findings will be further investigated in a new clinical trial slated to begin in early 2023 with support from the National Cancer Institute. The phase 3 study will include approximately 1900 children and adults between 5 and 60 years of age with medium- and low-risk HL who will be tracked for 12 years to monitor their progress.

The investigators will evaluate whether the combination of BV and the immunotherapy nivolumab can prolong progression-free survival and further reduce patients’ exposure to standard chemotherapy and radiation. The patients will be followed for 12 years to monitor their progress and test the results.

Allison Brashear, MD, vice president for Health Sciences at the University at Buffalo and dean of the Jacobs School of Medicine and Biomedical Sciences, added that the results of the study “mean a greatly improved quality of life for the most vulnerable and courageous patients—children with cancer.”

“As one of the largest demonstrations of a successful immuno-oncologic approach in children with cancer, it is a powerful example of what happens when extraordinary institutions decide that collaboration is key to their success,” Brashear said in a press release.

REFERENCE

Pediatric multicenter study shows targeted therapy for high-risk Hodgkin lymphoma reduces relapse. EurekAlert! November 2, 2022. Accessed November 3, 2022. https://www.eurekalert.org/news-releases/970098