Efficacy of brentuximab consolidation by metabolic response in an international real‐world cohort of classic Hodgkin lymphoma at high risk for progression after ASCT

Background: Salvage chemotherapy and autologous stem cell transplant (ASCT) have cure rates of 60–70% in relapsed refractory (R/R) classic Hodgkin lymphoma (cHL). Pre-ASCT compete metabolic response (CMR) compared to partial metabolic response (PMR), is associated with significantly better progression free survival (PFS) and overall survival (OS). Post-ASCT brentuximab vedotin (BV) consolidation improves PFS in pts with high-risk relapse as per ATHERA criteria: early relapse [ER], primary refractory disease [PRD] or extra nodal disease (END). Impact of BV consolidation by pre-ASCT PET-based response is not well characterized. Here we report outcomes of BV consolidation on PFS and OS by pre-ASCT PET-based response in real world cohort of R/R cHL. Methods: From a multicenter, international, observational cohort of 15 institutions of US and Czech Republic, adult pts with cHL and high-risk relapse per ATHERA criteria, who had ASCT were included in this study. Demographics, time to relapse, extranodal disease, B symptoms, stage, lines of salvage therapies, ASCT era, BV consolidation were collected. Pre-ASCT metabolic response was determined institutionally according to PET-based Lugano criteria. Study objectives were PFS and OS from date of ASCT. Association of BV consolidation with PFS and OS was assessed in the subgroup of pre-ASCT CMR and PMR using propensity score weighted analysis. Results: Out of 1158 pts enrolled from January 2011 to December 2020, 880 met ATHERA criteria. Median age was 32 (12–72), 473 (54%) were male, 511 (59%) had advanced stage, 389 (45%) had END, 385 (45%) had B symptoms, 266 (30%) had PRD, 484 (55%) had ER, and 259 (29%) required ≥2 line of salvage pre-ASCT. 527 (60%) had CMR and 222 (25%) had PMR pre-ASCT. 208 received BV consolidation. Median follow up was 37 (0.3–137) months. In all pts, 2-yr PFS was 64% (CI95: 61–68) and OS was 90% (CI95: 88–93). Receipt of BV consolidation was associated with significantly higher 2 yr PFS (HR: 0.7, CI95: 0.5–0.9, p = 0.0002) and OS (0.4, CI95: 0.1–0.9, p = 0.0002) compared with no BV maintenance. In univariate analysis, increasing age and salvage therapy lines, ER, PRD, END, accounting for age, relapse <12 months, PRD, extranodal disease, salvage therapy lines and ASCT era, BV consolidation was not significantly associated with PFS (0.7, CI95: 0.4–1.2, p = 0.1) or OS (0.5, CI95: 0.2–1.4, p = 0.2) in the group of pts with pre-ASCT CMR. In pts with pre-ASCT PMR, BV consolidation was associated with higher PFS (0.5, CI95: 0.3–0.9, p = 0.01) and OS (0.4, CI95: 0.1–0.8, p = 0.02). The research was funded by: Czech Republic dataset was supported by grant NU22-03-00182 Keyword: Hodgkin lymphoma Conflicts of interests pertinent to the abstract. S. H. Desai Honoraria: Seattle Genetics K. A. Blum Research funding: BMS and Seattle Genetics