Targeted therapy for children with high-risk Hodgkin lymphoma reduces relapse rates, study shows

Targeted therapy for children with high-risk Hodgkin lymphoma reduces relapse rates, study shows

A targeted therapy for children with high-risk Hodgkin lymphoma (HL) has been shown to significantly reduce relapse rates when tested in a large multicenter clinical trial conducted by the Children's Oncology Group (COG) and led by pediatric oncologists at Roswell Park Comprehensive Cancer Center. Children's Healthcare of Atlanta and Winship Cancer Institute of Emory University. Combining the targeted antibody drug conjugate (ADC) brentuximab vedotin (BV) with standard chemotherapy made children 10% less likely to relapse. The results were published today in the New England Journal of Medicine (NEJM).

We saw a 10% improvement in event-free survival -; a real breakthrough. That's a pretty big win, especially in this area. We anticipate that this regimen will soon become the standard of care for pediatric patients with high-risk Hodgkin lymphoma.”

Kara Kelly, MD, senior study author

Kara Kelly, MD, is chair of the Roswell Park Oishei Children's Cancer and Blood Disorders Program and the Waldemar J. Kaminski Endowed Chair in Pediatrics at Roswell Park, as well as division chief of hematology/oncology in the Department of Pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo

The AHOD1331 clinical trial (NCT02166463) was funded by the National Cancer Institute (NCI) of the National Institutes of Health and conducted at 153 COG sites. The study was also supported by Seagen, formerly known as Seattle Genetics, and the St. Baldrick’s Foundation. The study was sponsored by the Division of Cancer Treatment and Diagnosis, NCI, and brentuximab vedotin was provided by Seagen under a cooperative research and development agreement with NCI.

“This study reflects a paradigm shift for advanced-stage Hodgkin's lymphoma in children and the introduction of the first targeted approach for the first-line treatment of pediatric Hodgkin's lymphoma and the first new regimen in two decades,” said study lead author Sharon Castellino, MD, MSc, director of the Leukemia and Lymphoma Program at the Aflac Cancer and Blood Disorders Center of Children's Healthcare in Atlanta, professor of pediatrics at Emory University School of Medicine and a research fellow at the Winship Cancer Institute at Emory University. Dr. This year, Castellino succeeded Dr. Kelly as COG Hodgkin Committee Chair. “We are optimistic that this study will pave the way for FDA approval of this targeted antibody-drug conjugate for children and adolescents.”

Study co-chair and co-author Dr.

HL is the most common cancer in patients aged 12 to 29 years. Although it has a high five-year survival rate -; 97% of those under 19 live five years after diagnosis -; about a third of survivors are considered high risk; Of these, around 15-20% suffer a relapse.

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The COG Study -; the largest and only randomized Phase 3 trial of the CD-30-targeting ADC ever conducted in newly diagnosed high-risk pediatric HL patients; included 587 patients aged 2-21 years with previously untreated disease.

Patients were randomly assigned to one of two arms, with both arms treated 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. Brentuximab Vedotin (BV) is an antibody-drug conjugate that specifically targets and destroys the CD30 protein on the surface of HL cancer cells while largely sparing healthy cells.

Both groups received on-site radiotherapy based on responses assessed after two cycles of treatment.

Follow-up approximately three and a half years after treatment showed 92.1% event-free survival in the brentuximab vedotin group compared with 82.5% in the control group; an overall risk reduction of 59% for relapse, death or a second malignancy.

A lower risk of relapse could potentially eliminate the need for retreatment with additional toxic therapies. In the long term, the toxicity of treatment places HL survivors at very high risk of breast cancer, stroke, myocardial infarction, restrictive lung disease, infertility, and shortened lifespan.

“Brentuximab vedotin is not expected to have long-term toxicity,” says Dr. Kelly, noting that during the treatment phase of the clinical trial, fewer than 10% of patients who received it required a dose reduction. “As the drug could be administered more consistently, its effectiveness improved without an increase in neuropathy or serious infections.”

Dr. Kelly, Dr. Castellino and colleagues will build on these findings in a new clinical trial scheduled to begin in early 2023 with support from the National Cancer Institute. The randomized Phase 3 trial will enroll approximately 1,900 children and adults ages 5 to 60 years with intermediate- and low-risk HL. The goal: to determine whether the combination of the CD30-targeting ADC brentuximab vedotin and the immunotherapy drug nivolumab can extend progression-free survival and further reduce patients' exposure to standard chemotherapy and radiation. Patients will be followed for 12 years to monitor their progress and measure outcomes.

Allison Brashear, MD, vice president for health sciences at the University at Buffalo and dean of the Jacobs School of Medicine and Biomedical Sciences, says the study's results "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-oncology approach in children with cancer,” notes Dr. Brashear, “it is a powerful example of what happens when exceptional institutions decide that collaboration is the key to their success.”

Lucky Jain, MD, MBA, pediatrician-in-chief at Children's Healthcare of Atlanta and chair of the Department of Pediatrics at Emory University School of Medicine, said, "A 10 percent reduction in recurrences in children with high-risk Hodgkin's lymphoma is a significant milestone for the pediatric cancer field. Children's Healthcare of Atlanta and Emory University are proud of this incredible leap forward led by our physicians, Dr. Sharon Castellino and Dr. Frank Keller, along with their staff and the Children’s Oncology Group.”

Source:

Roswell Park Comprehensive Cancer Center

Reference:

Castellino, SM, et al. (2022) Brentuximab vedotin with chemotherapy in high-risk pediatric Hodgkin lymphoma. New England Journal of Medicine. doi.org/10.1056/NEJMoa2206660.

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