Relapsed/Refractory Hodgkin lymphoma after first-line escalated beacopdac: Adverse outcomes are overcome by use of second-line targeted therapy - an international real-world analysis

Abstract

Abstract Introduction Escalated (e) BEACOPP is a well-established treatment option for advanced and intermediate-stage Hodgkin Lymphoma (HL). The eBEACOPDac regimen, which replaces procarbazine with dacarbazine, is favoured in some countries due to reduced gonadal and hematologic toxicity, with similar survival rates (Santarsieri, Lancet Oncol 2025). Both regimens offer very high cure rates but there are limited data on the efficacy of second line (2L) chemotherapy in patients who relapse or are refractory (R/R) to first line (1L) eBEACOPP and no data for patients treated with eBEACOPDac. This international, real-world analysis assessed the efficacy of 2L treatment in patients with R/R HL after 1L eBEACOPDac. Methods Data were collected from 15 centres across the UK and France between December 2018 and March 2024. All patients had R/R classical HL following 1L escBEACOPDac (i.e. as first cycle of HL treatment, in line with HD18, HD17 or AHL2011 protocols) and received 2L treatment with intent to consolidate with stem cell transplant (SCT). The primary endpoint was progression-free survival (PFS), measured from the start of 2L therapy. Results A total of 72 patients were included, with a median age of 25 yrs (range 16-56); 64% were male. Patients received 1L eBEACOPDac in line with following regimens: HD18 n=46, HD17 n=13, AHL2011 n=13. Prior to 2L treatment, 47% had stage IV HL, 54% had primary refractory disease and 46% relapsed >3 months after first line treatment, with a median time to relapse of 9.0 months (range 3.25 - 64.6). Most patients received conventional combination 2L chemotherapy (chemo, n=55; 76%), with gemcitibine, dexamethasone and cisplatin (GDP) most frequently used (n=48; 67%). 17 patients (24%) received 2L targeted agents: pembro-GVD (n=8), BV-DHAC (n=5), BV-nivo (n=2), pembro-ICE (n=1) and Brentuximab Vedotin (BV) monotherapy (n=1). The overall response rate to 2L treatment was 69%, with 46% achieving complete response. 35 patients (49%) proceeded directly to autologous SCT (ASCT) after 2L treatment. Median follow up after 2L treatment is 18.4 months (range 3.3-73.4) with a 1-yr PFS 56.9% (95% CI: 46.2 - 70.0) and 2-yr PFS of 42.5% (95% CI: 30.5 - 59.3. For patients receiving ASCT after 2L treatment, 1-year PFS was 85.7%, (95% CI: 73.7 - 99.7). For the whole cohort, 1-year overall survival (OS) was 98.4% (95% CI: 95.4 - 100) and 2-year OS was 93.2% (95% CI: 85.7 - 100). 3 deaths occurred, 2 due to SCT toxicity and 1 due to HL. The only variable associated with outcomes was use of 2L targeted agents. There was no clear association between PFS and primary refractory status, stage IV disease, extranodal disease, haemoglobin, maximum tumour diameter or number of 1L eBEACOPDac cycles in this cohort. Patients receiving targeted agents were slightly older than with 2L chemo (28 years vs 23, p=0.02) and were more likely to have received an AHL2011 approach: 10 patients (58.8%) had received ≤2 cycles of first line eBEACOPDac, vs 9 (16.4%) receiving chemo. ASCT rates after 2L targeted agents were higher: 13 patients (76%) vs 22 (40%) with chemo. Of those who received 2L targeted agents 12 patients (92.3%) received post-SCT maintenance, all receiving BV except 1 receiving pembrolizumab. The 2-year PFS for patients receiving targeted treatment was 79.1%, (95% CI: 56.3 - 100) vs 32.3% (95% CI: 20.4 - 51.1) for chemo. For patients receiving 2L chemo after eBEACOPDAc, PFS rates were lower than seen in a similar cohort of HL patients treated with 2L chemo after 1L ABVD, where 2-yr PFS was 54% (Shotton et al, ICML 2021) Conclusions For R/R HL after 1L eBEACOPDac, patients treated with 2L chemo have inferior outcomes compared to patients who relapse after ABVD. This informs our discussions with patients who relapse after 1L eBEACOPDac when consenting to 2L treatment. The use of 2L targeted agents was associated with substantially better outcomes, with a 47% difference in 2-yr PFS, which is unlikely to be attributable to differences in baseline characteristics alone. Longer follow-up is needed to assess any impact on OS. With increasing use of intensive 1L regimens such as eBEACOPDac globally, 2L access to targeted agents is critical for the effective management of R/R HL.