Impact of Novel Therapies on the Efficacy of Post-Transplantation Brentuximab Vedotin Maintenance in Hodgkin Lymphoma

Use of brentuximab vedotin (BV) and PD-1 monoclonal antibodies (mAbs) before autologous stem cell transplantation (ASCT) could impact the benefit of post-ASCT BV maintenance in relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL). We identified 1091 patients with R/R cHL who underwent ASCT between 2010-2022. In total, 244 (22%) received a PD-1 mAb and 443 (41%) received BV before ASCT, while 305 (28%) received BV maintenance. We performed 1:1 propensity score matching to assess the efficacy of BV maintenance in different patient subgroups. Among 608 matched patients, the 3-year progression-free survival (PFS) and overall survival were 73% (95%CI 70-78) and 95% (95%CI 93-97), respectively. BV maintenance was associated with improved PFS for patients with no exposure to novel agents, especially those with 2+ modified AETHERA risk factors (0-1 factors, HR 0.51 ([95%CI 0.24-1.09], p=0.083; 2+ factors, HR 0.40 [95%CI 0.25-0.65], p<0.001). In contrast, BV maintenance was not associated with a significant PFS benefit for any patient subgroup who received novel agents before ASCT (BV-treated, 0-1, HR 1.43 [95%CI 0.53-3.81], p=0.48; 2+ HR 0.79 [95%CI 0.34-1.82], p=0.58; PD-1-treated, 0-1 (p>0.99), 2+ HR 0.25 [95%CI 0.03-2.14), p=0.21). In particular, we observed excellent outcomes for patients undergoing ASCT in a complete response after one line of PD-1-based salvage treatment with no significant benefit for BV maintenance observed (2-year PFS 100% vs 95%, p>0.99). The benefit of BV maintenance appears to be attenuated for patients receiving novel agents with salvage therapy. Omission of BV maintenance should be considered for patients anticipated to have excellent outcomes.