A targeted therapy has significantly reduced relapse rates among children with high-risk Hodgkin’s lymphoma (HL) in a multicenter clinical trial. Patients who received the targeted antibody-drug conjugate (ADC) brentuximab vedotin (BV), with the standard chemotherapy regimen, were 10% less likely to relapse. The findings were published in the New England Journal of Medicine (NEJM).
“This trial reflects a paradigm shift for advanced-stage Hodgkin lymphoma in children, and an introduction of the first targeted approach for initial therapy in pediatric Hodgkin lymphoma and the first new regimen in two decades,” says study first author Sharon Castellino, MD, MSc, Director of the Leukemia and Lymphoma Program at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta.
“We saw a 10% improvement in event-free survival—a real breakthrough,” says study senior author Kara Kelly, MD, Chair of the Roswell Park Oishei Children’s Cancer and Blood Disorders Program. “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.”
HL is the most common cancer in patients 12-29 years old. Although it has a high five-year survival rate—97% of those under 19 are alive five years after diagnosis—about one-third of survivors are classified as high risk; of those, approximately 15-20% will relapse.
The COG study—the largest and only randomized phase III trial with the CD-30 targeted ADC ever conducted with newly diagnosed high-risk HL pediatric patients—involved 587 patients ages 2-21 with previously untreated disease.
Patients were randomized to one of two arms, both arms receiving treatment over five 21-day cycles. Those in the control group received the standard pediatric chemotherapy regimen. The second group received the standard pediatric chemotherapy regimen, plus brentuximab vedotin, which is an antibody-drug conjugate that specifically targets the CD30 protein on the surface of HL cancer cells.
Both groups received site radiation therapy based on responses assessed after two cycles of treatment.
Follow-up at about three and a half years after treatment showed 92.1% event free survival in the brentuximab vedotin group, compared with 82.5% for the control group—an overall risk reduction of 59% of relapse, death or a second malignant neoplasm.
Lower risk of relapse could possibly eliminate the need for re-treatment with additional toxic therapies. Over the long term, treatment toxicity puts HL survivors at very high risk of breast cancer, stroke, myocardial infarction, restrictive pulmonary disease, infertility and shortened lifespan.
“Brentuximab vedotin is not anticipated to have long-term toxicity,” added Kelly, noting that during the treatment phase of the clinical trial, less than 10% of patients who received it needed a dose reduction. “Because the drug could be given more consistently, its efficacy improved with no increase in neuropathy or serious infection.”
“The demonstration of the effectiveness of a highly targeted treatment directed against the malignant cell population in newly diagnosed pediatric and young adult patients with high-risk Hodgkin lymphoma is a significant step forward toward improving cure rates and may do so without adding significant long-term toxicity for this young population with many years of life remaining,” said Adds Frank Keller, MD, a co-author and Pediatric Hematologist/Oncologist at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta and Professor of Pediatrics at Emory University School of Medicine.
