BENDAMUSTINE SUPERCHARGE PLUS BRENTUXIMAB VEDOTIN AS EARLY SALVAGE FOLLOWING FAILURE OF 2 ABVD CYCLES IN HL: LONG-TERM RESULTS OF A RETROSPECTIVE MULTICENTER STUDY

Treatment intensification with salvage therapy, and high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) is the best course of action for patients aged ≤ 60 years with classic Hodgkin lymphoma (c-HL) who fail to obtain complete metabolic remission (CMR) to first-line therapy. However, the clinical impact of early treatment intensification in patients showing positron emission tomography (PET)-positive evaluation after two cycles of ABVD remains to be confirmed. Theoretically, sequential brentuximab vedotin and bendamustine supercharge, that is, Bv+Bs₂₁, as 3-day outpatient i.v. infusions of 1.8 mg/kg Bv on day 1 and Bs on days 2 and 3 at a fixed dose of 120 mg/m²/day, is a promising salvage regimen in this setting. We carried out a multicenter retrospective study (NCT06295211) including 50 adult patients with c-HL who had PET-positive (Deauville scale score ≥ 4) scans after two cycles of ABVD from 1 September 2013 to 1 September 2023. In all, 46 of the 50 collected patients were enrolled (median age, 37 years; range, 19–60). In fact, 42 cases received the four 3-week courses of Bv+Bs₂₁ followed by ASCT, four cases received the scheduled Bv+Bs₂₁ regimen without ASCT (patient’s decision), and four patients were excluded for alternative salvage regimens (n = 3) and insufficient information (n = 1). The primary endpoint was 5-year progression-free survival (PFS) calculated for patients receiving four courses of Bv+Bs₂₁ plus HDT and ASCT, and for those who received only four courses of Bv+Bs₂₁. Secondary endpoints were the overall response rate, overall survival (OS), toxicity, peripheral blood stem cell (PBSC) collection and bridge to transplant, and feasibility of Bv+Bs21 regimen. With a median follow-up of 60 months (range, 7–132 months), the overall enrolled population PFS rate was 82% (86% for patients undergoing ASCT and 50% for those not receiving ASCT). The PFS stratified according to the pre-salvage treatment FDG-PET was 100% for DS score of 4 (n = 12) and 78% for DS score 5 (n = 34). With a median follow-up of 60 months, the 5-year OS rate of the entire analyzed population was 90%. After Bv+Bs₂₁ regimen, 42 patients obtained CMR and four partial metabolic remissions, with a rate of overall response of 100%. PBSC mobilization and harvest were successful in all cases, with a median CD34+ cells/kg yield of 4.1 × 10⁶ (range, 1.9–5.1 × 10⁶). Overall, the most common adverse events were hematological of any grade, while, due to the specific premedication against acute toxicity during the i.v. administration of Bv+Bs₂₁, serious infusion related reactions occurred only in three patients. All patients were efficacy-evaluable patients having completed four courses of Bv+Bs₂₁: ≤ 10% of patients received < 85% of the planned treatment. In our study, early treatment intensification with Bv+Bs₂₁ followed by HDT and ASCT obtained excellent outcomes in high-risk patients with c-HL with interim PET-positive scans after two ABVD courses.

Keywords: combination therapies; combination therapies; Hodgkin lymphoma

No potential sources of conflict of interest.