Abstract T087

Progression-Free Survival (PFS) with Nivolumab-AVD is superior to Brentuximab Vedotin-AVD with 2-year follow-up of S1826 in Adolescent Advanced Stage (AS) Classic Hodgkin Lymphoma (cHL)

Background: While Brentuximab vedotin (BV) combined with dose-dense chemotherapy and response-based involved site radiation therapy (RT) is efficacious in pediatric patients (pts) with high-risk cHL, PD-1 inhibitors have not been evaluated in the frontline setting in adolescents with cHL. We present the 2-year (y) follow-up of adolescents treated on S1826, a randomized, phase 3 trial comparing nivolumab (N)-AVD vs. BV-AVD in newly diagnosed advanced stage (AS, Stage 3-4) cHL.

Methods: Eligible pts were randomized 1:1 to 6 cycles of N-AVD or BV-AVD. At randomization, pts were stratified based on age, international prognostic score (IPS), and intent to use RT for residual metabolically active lesions at the end of treatment. The primary endpoint was progression free survival (PFS); secondary endpoints included overall survival (OS), event-free survival (EFS), and safety.

Results: 24% (n=240) of 994 pts enrolled on S1826 were 12-17 y. Among 236 eligible pts randomized to N-AVD (n=118) or BV-AVD (n=118) the median age was 15.6 y (12-17.9 y), 51% of pts were male, 68% were white, 15% were black, and 17% were Hispanic. 57% had Stage IV disease, 43% had bulky disease and 28% had an International Prognostic Score (IPS) score of 4-7 with no difference by study arm. At 2 y follow-up, the PFS was 95% with N-AVD and 83% in BV-AVD [HR 0.32, 95% CI 0.14-0.76] (Fig). EFS was 91% with N-AVD vs. 81% with BV-AVD (p=0.02). Overall use of protocol-specified RT was 1.3% (n=1 N; n=2 BV). OS did not differ by treatment arm with 1 death reported at 21 days from registration in a patient on BV-AVD. The rate of grade (gr) ≥ 3 neutropenia was 44% after N-AVD compared to 39% after BV-AVD; however, only 3% of pts had gr ≥ 3 febrile neutropenia and 1% with sepsis after either regimen. Differences in use of GCSF (64% N; 97% BV) reflected protocol mandated GCSF with BV. Overall rates of immune related adverse events (AEs) (any gr) were low. Hypo/hyperthyroidism (any gr) was more frequent after N-AVD (5%/2% N vs.1%/0%, BV). Sensory peripheral neuropathy (> gr.2) was more frequent after BV-AVD (7%, N vs. 14%, BV). 80% of adolescent pts received dexrazoxane. AE associated discontinuation of N or BV as part of therapy occurred in 4.2% and 0.8% of patients respectively.

Conclusions: N-AVD is well tolerated in adolescents 12-17 y, with high PFS and EFS and minimal use of RT compared to prior pediatric HL studies. N-AVD is a new standard of care for adolescents with AS cHL.

Authors

Sharon M. Castellino, Hongli Li, Alex F. Herrera, Angela Punnett, Michael Le, Susan K. Parsons, Frank G. Keller, Richard Drachtman, Adam Lamble, Christopher J. Forlenza, Andrew Doan, Sarah Rutherford, Andrew Evens, David Hodgson, Richard F. Little, Malcom Smith, Hildy Dillon, Joo Song, Sonali Smith, Jonathan W. Friedberg, Kara M. Kelly