NEJM Publishes Two Major Papers by Pediatrics Faculty

By Ellen Goldbaum

While co-authoring a NEJM paper by itself signifies that the findings are groundbreaking, the papers by the University at Buffalo co-authors are having an even more powerful impact: each reported significant positive benefits from the intervention being studied.

“The fact that the New England Journal of Medicine published clinical trial results by two of our extraordinary physician-scientists and alumnae who happen to be in the same department unequivocally demonstrates that Jacobs School research is fundamentally transforming the standard of care,” says Allison Brashear, MD, MBA, UB’s vice president for health sciences and dean of the Jacobs School. “Western New York parents enrolled their children in these studies, experiencing firsthand how our community benefits directly from UB clinical trials.”

On Nov. 2, Lucy D. Mastrandrea, MD ’99, PhD ’99, associate professor of pediatrics, chief of the department’s Division of Endocrinology/Diabetes and a physician with UBMD Pediatrics, was a co-author on the NEJM study that found that a weekly injection of the drug semaglutide plus lifestyle intervention resulted in a mean percent reduction body mass index (BMI) of 16.1% in teens.

This combination treatment resulted in a greater reduction in BMI than lifestyle intervention alone. About 40% of these adolescent patients attained normal weight. These semaglutide-treated patients also had improvement with respect to cardiometabolic risk factors.

While the drug is widely used for diabetes control and weight loss in adults, it has yet to be approved for teens. The results were better than anything the participants or even the researchers had anticipated.

“This is a major advance,” says Steven E. Lipshultz, MD, A. Conger Goodyear Professor and Chair of pediatrics in the Jacobs School and president of UBMD Pediatrics. “It’s groundbreaking and potentially life-changing because it suggests that sustained improvement in weight is more likely when you combine anti-obesity medication with lifestyle interventions. If you intervene in adolescence, you have a greater chance to break that obesity cycle.

“This gives hope to adolescents with obesity to be able to successfully adhere to recommendations for weight loss, achieve their goals, and improve their quality of life and overall health,” he continues. “With nearly one in five children globally affected by obesity, watchful waiting for teens to improve with lifestyle interventions alone is often not an acceptable option. Based on the results of this groundbreaking study, it is clear that this anti-obesity therapy in conjunction with lifestyle intervention will be a welcome addition to the current standard of care.”

On Nov. 3, the NEJM published a paper that described how children with high-risk Hodgkin lymphoma responded to a targeted therapy for the disease that has been effective in adults.

Kara M. Kelly, MD ’89, professor of pediatrics and chief of the department’s Division of Hematology/Oncology and chair of the Roswell Park Oishei Children’s Cancer and Blood Disorders Program, was senior author on the study. She sees patients at UBMD Pediatrics.

The trial — conducted by the National Cancer Institute-supported Children’s Oncology Group and led by pediatric oncologists at Roswell Park Comprehensive Cancer Center, Children’s Healthcare of Atlanta and Winship Cancer Institute of Emory University — found that the multiagent chemotherapy, including brentuximab vedotin, was shown to significantly reduce relapse rates when tested in a large multicenter clinical trial when compared to conventional multiagent chemotherapy that did not include brentuximab vedotin. In addition, in the brentuximab vedotin arm, there was a 59% lower risk of an event or death, and no increase in the incidence of toxic effects at 3 years.

Just a week later, Kelly and her co-authors got word that, based on the results of this trial, the FDA has now approved the pediatric usage of brentuximab vedotin for treating pediatric Hodgkin lymphoma, the first pediatric approval for this drug.

Lipshultz says such approvals are particularly noteworthy.

“When I was a voting member on the FDA Oncology Drugs Advisory Committee, it had approved about 20 new drugs for adults over the preceding 10 years,” he recalls. “But over those same years, only two new cancer drugs were approved for kids. For very obvious reasons, those approvals are much more difficult to get. That’s why having brentuximab vedotin being approved by the FDA for children with Hodgkin lymphoma is such a big deal.”

He concludes: “Journal papers very often get published that report observations but don’t have the potential to immediately change clinical care. But both of these are groundbreaking studies that can immediately change clinical management and care of children and adolescents if implemented. Each involved prospective clinical trials with randomization and the results of each trial can immediately change practice, ultimately leading to better health for children and adolescents.”