Nivolumab-AVD superior to brentuximab vedotin-AVD for advanced stage Hodgkin lymphoma

Treatment with nivolumab (N) plus doxorubicin, vinblastine, and dacarbazine (AVD) leads to improved progression-free survival (PFS) relative to brentuximab vedotin (BV) plus AVD in patients with advanced stage classic Hodgkin lymphoma (HL), according to the results of the SWOG S1826 study, which was presented at the recent ASCO 2023.

In addition, only a few immune-related adverse events (AEs) have been reported, and <1 percent of the patients have received radiation therapy (RT). However, a longer follow-up is necessary to assess both the overall survival (OS) and patient-reported outcomes (PROs).

“S1826, the largest HL study in National Clinical Trials Network (NCTN) history, is a key step towards harmonizing the paediatric and adult treatment of AS HL,” said the researchers, led by Alex Francisco Herrera from the City of Hope National Medical Center in Duarte, California, US.

Herrera and his team enrolled a total of 994 patients with stage 3‒4 HL aged >12 years in this study between 2019 and 2022. Of these, 976 met the eligibility criteria and were randomized 1:1 to receive six cycles of either N-AVD (n=489) or BV-AVD (n=487). Those who received BV-AVD were required to receive granulocyte colony-stimulating factors prophylaxis vs optional with N-AVD.

Notably, “[p]respecified patients could receive RT to residually metabolically active lesions on end-of-treatment positron emission tomography,” according to the researchers, who stratified patients by age, international prognostic score (IPS), and intent to use RT.

Herrera and colleagues then evaluated response and disease progression using the 2014 Lugano Classification. PFS was the primary endpoint, while secondary ones included OS, event-free survival, PROs, and safety.

Of the eligible patients (median age 27 years), 56 percent were male, 76 percent were White, 12 percent were Black, and 13 percent were Hispanic. In terms of age, 24 percent were <18 years old and 10 percent were >60 years old. Additionally, 32 percent had IPS of 4‒7, and <1 percent had received RT. [ASCO 2023, abstract LBA4]

“At the planned second interim analysis (50 percent of total PFS events), the SWOG Data and Safety Monitoring Committee recommended to report the primary results because the primary PFS endpoint crossed the protocol-specified conservative statistical boundary,” according to the researchers.

Better survival

Fewer PFS events were observed after N-AVD compared with BV-AVD (30 vs 58 events, respectively). Over a median follow-up of 12.1 months, the N-AVD arm demonstrated superior PFS (hazard ratio, 0.48, 99 percent confidence interval, 0.27‒0.87; one-sided p=0.0005; 1-year PFS of N-AVD vs BV-AVD: 94 percent vs 86 percent).

More deaths occurred after BV-AVD compared with N-AVD (11 vs 3 deaths). Among these deaths, seven and three were due to AEs, respectively. Grade ≥3 haematologic AE was 48.4 percent (45.1 percent grade ≥3 neutropenia) after N-AVD vs 30.5 percent (23.9 percent grade ≥3 neutropenia) after BV-AVD.

Similar rates of febrile neutropenia (N-AVD vs BV-AVD: 5.6 percent vs 6.4 percent), pneumonitis (2.0 percent vs 3.2 percent), alananine transaminase elevation (30.7 percent vs 39.8 percent), and colitis (1 percent vs 1.3 percent) were observed.

Finally, patients in the N-AVD arm were more likely to have hypo/hyperthyroidism (N-AVD vs BV-AVD: 7 percent/3 percent vs <1 percent), while those in the BV-AVD arm had greater odds of peripheral neuropathy (sensory: 28.1 percent vs 54.2 percent; motor: 4 percent vs 6.8 percent).

“The addition of BV to initial chemotherapy improves OS in adults and PFS in paediatric patients with AS HL,” the researchers said. “However, frontline BV adds toxicity, most paediatric patients receive RT, and 7‒20 percent of patients still develop relapsed/refractory HL.”