Nivolumab-AVD Boosts PFS in Untreated Hodgkin Lymphoma

CHICAGO — Adding the immune checkpoint inhibitor nivolumab (Opdivo), rather than brentuximab vedotin (Adcetris), to a standard chemotherapy backbone reduced the risk of disease progression or death in newly diagnosed adults and adolescents with advanced-stage classical Hodgkin lymphoma (cHL), according to the SWOG S1826 trial.

Patients in the phase III study received six cycles of doxorubicin (Adriamycin), vinblastine, and dacarbazine (AVD) plus either nivolumab or brentuximab. At 1 year, 94% of the patients in the nivolumab group were alive and free of disease progression versus 84% in the brentuximab group (HR 0.48, 99% CI 0.27-0.87, P=0.0005), reported Alex Francisco Herrera, MD, of City of Hope in Duarte, California.

“Traditionally, adults and children with advanced Hodgkin lymphoma in the United States have been treated with different chemotherapy regimens, and the majority of children also receive radiation treatment,” Herrera said at a press briefing at the American Society of Clinical Oncology annual meeting.

“As part of the design and planning of our trial, adult and pediatric cooperative groups [National Clinical Trials Network] met and arrived at a consensus on both the control and experimental regimens, with the goal of harmonizing the treatment of Hodgkin lymphoma across all ages, which is a truly unique outcome,” he explained.

Herrera pointed out that less than 1% of patients in both arms ultimately underwent radiation therapy, which is associated with second tumors and cardiac damage.

Patients in the nivolumab group were more likely to develop neutropenia (55% vs 32% in the brentuximab arm), but were less likely to require granulocyte colony-stimulating factor (G-CSF; 54% vs 95%, respectively). They also were less likely to experience bone pain (8% vs 20%) and neuropathy (29% vs 55%), and less likely to discontinue nivolumab than brentuximab vedotin (11% vs 22%).

There were 11 deaths in the brentuximab group (seven toxicity-related) and four in the nivolumab group (three related to adverse events).

The nivolumab-AVD regimen “is poised to be a new standard therapy for advanced-stage Hodgkin lymphoma,” Herrera said, adding that the trial met its primary endpoint for progression-free survival (PFS) improvement.

But more research is needed, cautioned Melissa Hudson, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee. Patients need follow-up to assess the long-term impact of the two regimens. “Both these agents show that patients respond to their use, and both are effective,” she told MedPage Today. “Whether one is better than the other, especially in the pediatric patient population, in the long-term still has to be determined.”

Herrera reported that nivolumab plus AVD was more effective in the adult groups, but that in children, the PFS difference was not statistically significant, although it trended in favor of the nivolumab arm:

• Ages 12-17 years: HR 0.48 (95% CI 0.18-1.27)
• Ages 18-60 years: HR 0.56 (95% CI 0.32-0.98)
• Over 60 years: HR 0.27 (95% CI 0.10-0.76)

Hudson, who was not involved in the study, noted that pediatricians are wary when it comes to adopting new treatments. She also said that insurance coverage plays a role in how quickly a new regimen is accepted.

SWOG S1826 assigned more than 976 patients to AVD plus either nivolumab or brentuximab vedotin. Patients had newly diagnosed stage III-IV cHL, and were stratified by age (12-17 years, 18-60; and >60), International Prognostic Score, stage, and by intent to use radiation treatment.

Median age was 27 years, 56% were male, and 76% where white. A little less than a quarter of the patients were children while 10% were over age 60. Patients assigned to the brentuximab arm were required to receive G-CSF while it was optional in the nivolumab arm.