Bendamustine in Combination with Gemcitabine and Vinorelbine (BEGEV) Is an Effective Regimen for Heavily Pretreated, Relapsed/Refractory Hodgkin Lymphoma Patients: A Multicenter, Retrospective Real-World Study

Abstract INTRODUCTION: The availability of novel monoclonal antibodies (moAbs) including the anti-CD30 Brentuximab Vedotin (BV) and the anti-programmed cell death-1 (anti-PD-1) Nivolumab and Pembrolizumab has introduced innovative options in the process of therapeutic decision making for relapsed/refractory classical Hodgkin lymphoma (R/R cHL). However, multiagent chemotherapy followed by autologous stem cell transplantation (auto-SCT) in chemosensitive patients still remains the standard-of-care treatment of R/R cHL. In a multicenter phase 2 study, the BEGEV (Bendamustine, Gemcitabine, Vinorelbine) regimen was previously reported as a highly effective treatment in the second-line salvage setting (Santoro et al., J Clin Oncol, 2016). Here, we report a retrospective analysis of efficacy and toxicity of the BEGEV regimen administered as second- or subsequent-line therapy to R/R cHL in a real-world setting. PATIENTS AND METHODS: From January 2013 to March 2018, 73 cHL patients (median age, 31 years; range, 16 - 69) were candidate to receive 4 courses of BEGEV as second-line (n= 50) or beyond second-line (n= 23) salvage therapy. Refractory patients were 56% in the second-line group and 78% in the group treated beyond second-line. This latter group received a median of 3 (range, 2-8) lines of therapy prior to BEGEV, including Brentuximab Vedotin (BV) (83%) and auto-SCT (43%). RESULTS: In keeping with the phase 2 study, hematological and non-hematological side effects were acceptable. In fact, 64 (88%) patients completed the planned treatment whereas only 9 (12%) patients experienced early therapy discontinuation due to progressive disease (n= 8) and sepsis (n= 1). Of 72 patients evaluable for response, 50 (69.4%) achieved complete remission (CR) and 7 partial remission (PR) with an overall response rate (ORR) of 79%; 1 patient experienced stable disease (SD) and 14 (19%) progressive disease (PD). All but one patient experiencing PD/SD were chemorefractory (14/15). The probability of achieving response (CR+PR) to BEGEV was significantly higher in chemosensitive vs chemorefractory patients (96% vs 70%, P=0.007) whereas no difference could be detected for patients receiving BEGEV as second-line vs those treated beyond second-line (84% vs 70%, P=0.217). All BEGEV responders (n=57) were offered SCT: 44 received auto-SCT, 9 allo-SCT and 1 tandem auto/allo-SCT; 1 patient is waiting for SCT, and 2 refused. With a median follow-up of 14 months, the 1-yr overall survival (OS) and progression-free survival (PFS) are 93% and 69%, respectively. Disease status (sensitive vsrefractory) at BEGEV had no impact on survival (1-yr OD: 94% vs 92%, P=0.57) likely due post-BEGEV consolidation therapy, whereas timing of BEGEV administraton (second-line vs subsequent-lines) significantly affected survival (1-yr OS: 97% vs 78%, P=0.018). CONCLUSION: Data from this real-world analysis further confirm that BEGEV is an effective and safe salvage treament in R/R cHL even when administered to heavily pre-treated patients, thus representing an optimal therapeutic platform prior to consolidation with SCT or immunotherapy. Disclosures Carlo-Stella: Sanofi: Consultancy; Genenta Science: Speakers Bureau; AstraZeneca: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Amgen: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; MSD Italia: Speakers Bureau; Boehringher Ingelheim Italia: Consultancy; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau.