Adcetris, an Antibody-Drug Conjugate, Shows Promise As a Treatment for Pediatric Hodgkin Lymphoma

Combining the targeted antibody-drug conjugate (ADC) brentuximab vedotin (BV) with the standard chemotherapy regimen resulted in a 10% improvement in event-free survival in high-risk Hodgkin lymphoma pediatric patients, according to new research.

Brentuximab vedotin is sold under the brand name Adcetris. Antibody-drug conjugates consist of an antibody that binds to cancer cells and, upon binding, the release of drug that targets and kills the cancer cells.

In addition to the 10% improvement, there was a 92% event-free survival in the brentuximab vedotin group over three years, compared with 82.5% for the control group, an overall risk reduction of 59% of relapse, death or a second malignant neoplasm, the researchers wrote in the New England Journal of Medicine

Sharon Castellino, M.D.

Sharon Castellino, M.D., director of the Leukemia and Lymphoma Program at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta and professor of Pediatrics at Emory University School of Medicine, and Kara Kelly, M.D., 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, were co-lead authors of the study.

The lower risk of relapse could possibly eliminate the need for re-treatment with additional toxic therapies. As a result, a cost effectiveness analysis of the approach is being conducted and will be a key point of the success of the trial, Castellino told Managed Healthcare Executive®.

“The fact that there was a 10% increase in anti-tumor effect in the trial arm compared to the standard arm is enormous. It means that only 8% of children are at risk for needing hematopoietic stem cell transplant, in contrast to 18% of children receiving the standard therapy without brentuximab vedotin and 18% of adults who were treated with the ECHELON 1 regimen,” Castellino said.

The 92% event-free survival rate at three years with the brentuximab vedotin-chemotherapy combination is the highest reported result to date among all randomized phase 3 trials conducted either for children and adults with advanced stage Hodgkin lymphoma, Kelly told Managed Healthcare Executive®. Only 8% of children are at risk for needing additional therapies such as high-dose chemotherapy with autologous stem cell transplant.

The researchers plans to evaluate the cost-effectiveness of the experimental approach compared with the standard of care treatment for pediatric Hodgkin lymphoma, Kelly said. The analysis is ongoing and being supported by a grant from the Leukemia Lymphoma Society.

“While brentuximab vedotin is an expensive medication, treatment for relapsed Hodgkin lymphoma carries significant costs. Relapsed treatment generally consists of high-dose chemotherapy followed by autologous stem cell transplantation — very expensive therapies,” Kelly noted

In addition, patients are at higher risk for subsequent relapses, thus incurring additional treatment costs, or they may be at risk for toxicity related to cancer treatment, resulting in a higher risk for second cancers, cardiovascular disease, strokes, pneumonitis and infertility, “all of which are associated with high medical costs,” Kelly noted.

“With the 10% reduction in relapses, we hypothesize that the new treatment which includes brentuximab vedotin will be found to be more cost effective,” Kelly said.

While the treatment is commercially available, it is not always covered by insurers for newly diagnosed Hodgkin lymphoma in children. SeaGen, one of the sponsors of the study, is seeking an FDA indication for children, the researchers said.

The research was funded by the National Cancer Institute and was supported by Seagen and the St. Baldrick’s Foundation. Conducted at 153 sites, it was the largest and only randomized phase 3 trial with this therapy, involving 587 patients ages 2 to 21 with previously untreated disease.

“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,” Castellino said in a news release. “We are optimistic that this trial will set the stage for FDA approval of this targeted antibody-drug conjugate for children and adolescents.”

The research team will also study brentuximab vedotin and another novel agent, Opdivo (nivolumab), in children, adolescents and young adults with early stage Hodgkin lymphoma. “The continued goal is to use targeted agents with precision and therefore reduce the historic chemotherapy and radiation approaches known to confer a risk of late effects in young patients as they age,” Castellino said.