Abstract T077

Nivolumab-AVD improves 2-year progression-free and overall survival compared to Bv-AVD in older patients aged ≥60 years with advanced stage classical Hodgkin lymphoma (cHL) enrolled on SWOG S1826

Background: Older patients (pts) with cHL have lower survival than younger pts. We previously reported early improved efficacy and tolerability of nivolumab (N)-AVD over brentuximab vedotin (Bv)-AVD in older pts on the randomized phase 3 trial, S1826. We present 2-year (y) follow up of pts ≥60y.

Methods: In this subset analysis, eligible pts were ≥60y with stage 3-4 cHL. Pts were randomized 1:1 to 6 cycles of N-AVD or Bv-AVD. G-CSF was required with Bv-AVD. Response was assessed by investigators using 2014 Lugano Classification. Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), event-free survival (EFS), and toxicity events.

Results: 103 pts ≥60y were enrolled from 7/9/19-10/5/22; 99 were eligible and randomized to N-AVD (n=50) or Bv-AVD (n=49). Median age was 66y (range, 60-83y), 63% male, 85% white, 4% black, 9% Hispanic, 60% stage IV, 44% IPS 4-7. At 2.1y median follow up, PFS, OS, and EFS were superior for N-AVD over Bv-AVD in this subset analysis. For N-AVD vs Bv-AVD, 2y PFS was 89% and 64% (HR 0.24, 95% CI 0.09-0.63, 1-sided stratified logrank p=0.001), 2y OS 96% and 85% (HR 0.16, 95% CI 0.03-0.75 stratified 1-sided logrank p=0.005), and 2y EFS 89% and 58% (HR 0.18, 95% CI 0.07-0.47, stratified 1-sided logrank p<0.001). On N-AVD, there were 3 deaths (2 infection/sepsis, 1 hepatic failure) and 4 progressions/relapses; on Bv-AVD, there were 10 deaths (5 infection/sepsis, 2 lymphoma, 1 cardiac arrest, 1 pneumonitis, 1 second malignancy) and 9 progressions/relapses. Non-relapse mortality was 6% with N-AVD and 16% with Bv-AVD. All treatment was discontinued early in 5 pts (10%) on N-AVD and 16 (33%) on Bv-AVD. Most common reasons for discontinuation (N vs Bv) were adverse events (AEs) (2 and 7 pts) and death (1 and 5 pts). 7 (14%) on N-AVD and 25 (51%) on Bv-AVD had any discontinuation of N and Bv, respectively. Despite more neutropenia with N-AVD, febrile neutropenia, sepsis, and infections were higher with Bv-AVD. The majority of AEs including peripheral neuropathy were more frequent with Bv-AVD. Hypothyroidism and rash were more frequent with N-AVD; other immune-related toxicity rates were similar between arms.

Conclusions: At 2y follow up, N-AVD improves PFS, OS, and EFS in cHL pts ≥60y. N-AVD is better tolerated than Bv-AVD; over half of pts discontinued Bv, primarily due to toxicity. N-AVD is a standard of care for older advanced stage pts fit for anthracycline-based combination therapy.