Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine for Advanced-Stage Classical Hodgkin Lymphoma

• With a median follow-up of 24.2 months, the 2-year PFS of patients treated with AN+AD was 88%

• AN+AD led to an 88% complete response rate and favorable safety profile, notable for the absence of febrile neutropenia

Treatment options for stage I/II bulky and advanced stage disease have recently extensively changed. For decades in North America, ABVD has been a frontline standard of care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared to ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (AN+AD) may improve efficacy and safety. This phase 2, open-label multi-part, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N=57), complete response (CR) and objective response rates were 88% (95% CI, 76.3 to 94.9) and 93% (95% CI, 83.0 to 98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4 to 26.9), the 2-year PFS rate was 88% (95% CI, 75.7 to 94.6); 88% (95% CI, 75.7 to 94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody-drug conjugate combination regimens in frontline advanced stage cHL is warranted. Trial registration: NCT03646123