Real world experience with brecadd protocol as frontline therapy for patients with advanced stage classical Hodgkin lymphoma: A multicenter retrospective study

Abstract Introduction: Traditionally, the management of patients with advanced-stage classical Hodgkin lymphoma (cHL) relied exclusively on chemotherapy. However, the advent of novel therapeutic agents such as brentuximab vedotin (BV) and integration into first-line regimens led to enhanced efficacy outcomes. This study retrospectively evaluates the clinical outcomes of advanced-stage cHL patients treated with the BrECADD protocol in real-world settings. Methods: This retrospective multicenter study analyzed data from 79 patients with cHL treated with the BrECADD protocol across 15 cancer centers in Israel. Patient demographics and disease features at baseline were characterized using descriptive statistics. Therapeutic responses were assessed per Lugano criteria, with response-evaluable patients defined as those who received at least one cycle of BRECADD chemotherapy. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves, with log-rank testing employed for statistical analysis. Results: Data collection for this multicenter retrospective study spanned July 1 2023 to July 1 2025, enrolling 79 patients across 15 Israeli medical centers. Among the cohort, 56% of patients were male, the median age was 30.0 years (range, 18–60) and 99% (78 patients) underwent pretreatment evaluation with PET-CT. Stage 2 disease was identified only in 7.6% (6 patients) and Stage IV disease was identified in 83% (64 patients). An International Prognostic Score (IPS) >2 was noted in 80% of the cohort (IPS available for 100% of patients). PET-2-guided treatment was employed in 99% of cases (78 patients). Negative PET-2 results were observed in 83% (65 patients), permitting completion of treatment after four cycles. Of the remaining 14 patients (17%), eight achieved complete metabolic response (CMR) after four cycles, and two reached CMR following six cycles. Among 79 response-evaluable patients, the overall response rate (ORR) and complete response (CR) rate following end of chemotherapy were 99% and 95%, respectively. At our cohort, only 3 patients (4%) underwent radiation therapy consolidation. At a median follow-up duration of 11.0 months (range: 2.1-31 months), PFS events recorded at 6.3%, corresponding to 5 documented cases of relapse in this cohort. All of them proceed to salvage treatment and alive, which bring the 1-year OS to 100%. Grade 4 hematological toxicities represented the most frequent adverse events, with grade 4 neutropenia and thrombocytopenia observed in 77% and 14% of patients, respectively. Peripheral neuropathy occurred in 24% of patients, of them only 3.8% with grade 3-4). Serious adverse events included two cases requiring ICU admission due to infectious complications and full recovery. 12 patients (15%) underwent any dose reduction in their treatment. Beside of them, 5 patients, based on physician discretion, underwent treatment de-escalation to the A-AVD protocol. Conclusion: This retrospective, multi-center, real world study of BrECADD protocol, characterized by robust data quality in most of the participants, demonstrated comparable efficacy and safety in treating advanced-stage cHL in real-world settings, aligning with outcomes reported in clinical trials. Notably, there was higher rate of CMR after 2 cycles of therapy (83%) and a markedly lower rate of radiation consolidation in this study compared to the pivotal trial (Borchmann, Peter et al, The Lancet, Volume 404, Issue 10450, 341 – 352).