Abstract P115

Outcomes in Double-Exposed Classical Hodgkin Lymphoma: The Impact of Treatment Sequence and Salvage Strategies After Brentuximab Vedotin and Checkpoint Inhibitor Failure

Background: Brentuximab Vedotin (BV) and checkpoint inhibitors (CPIs) revolutionized classical Hodgkin lymphoma (cHL) treatment, improving outcomes in both relapsed/refractory (RR) and primary treatment setting. The outcomes of patients (pts) with active disease after exposure to both agents are unclear and the impact of treatment sequencing is not well understood. We aimed to characterize RR-cHL pts with progressive disease (PD) after both BV/CPI to describe subsequent treatment outcomes, treatment sequencing and survival.

Methods: We conducted a retrospective analysis of RR-cHL pts with PD after treatment with BV and CPI (pembrolizumab or nivolumab) at Princess Margaret from 2012 to 2024. Patients exposed to both novel agents were classified as "Double Exposed" (DE).

Results: We identified 24 DE cHL patients with PD after treatment with sequential BV and CPI. Median age: 40 years (20-75 years); 62% male. 74% had received 4+ lines of therapy (median 4, 2-6) and 63% had undergone ASCT. Advanced stage: 83% - Extranodal disease: 62%. 71% were actively on treatment with a novel agent at PD (BV-CPI 81%, CPI-BV 100%, p=0.526). A trend in disparity of refractoriness to the most recent novel agent was observed (CPI-BV: 87.7%, BV-CPI: 50%, p=0.178) [Fig 1A]. Median follow-up was 37.9 months (3-121 mo); median overall survival (OS) was 46 mo for the entire cohort (7-121 mo). Median OS for subgroups: BV-CPI 46 mo; CPI-BV 12.5 mo (p=0.59). [Fig 1B]. The median progression-free survival (PFS) after the second agent was 7.4 mo (2-107 mo): BV-CPI 11.6 mo; CPI-BV 4.2 mo (p=0.0098) [Fig 1C]. Time to next treatment (TTNT) was longer for CPI-BV (35.41 vs 13.33 mo; p=0.025). 16 pts (67%) received further treatment while 8 (33%) went on to palliative therapy. Overall response rate (ORR) was 56% for pts receiving treatment with a variety of options used [Fig 1D].

Conclusions: DE BV/CPI pts represent a young, clinically aggressive, heavily treated RR- cHL population with progressive disease with poor outcomes. While the order of drug administration did not significantly impact OS, it may affect PFS and TTNT, highlighting the importance of studying treatment sequencing. With a proportion of pts transitioning to palliative care or not responding to subsequent therapy, BV/CPI DE pts have a need for novel treatment approaches. Our preliminary data underscore the critical need to optimize sequencing and salvage strategies to improve outcomes in this challenging population.