PF470 FIVE‐YEAR SURVIVAL AND DURABILITY RESULTS OF THE BEGEV REGIMEN FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) FOR RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA

Abstract

Background:There is a consensus that classical Hodgkin lymphoma (cHL) patients who are refractory to or relapse (R/R) after first‐line therapy may benefit of second‐line salvage treatment followed by autologous stem cell transplantation (ASCT) provided they are chemosensitive. As previously reported, the BEGEV (BEndamustine, GEmcitabine, Vinorelbine) regimen used as second‐line salvage therapy induces an objective response rate (ORR) >80% in R/R cHL, thereby resulting in a highly effective induction treatment before ASCT (Santoro et al., J Clin Oncol, 2016).Aims:Here, we assess safety, efficacy and durability results of the BEGEV regimen followed by ASCT after extended follow‐up (registered at www.clinicaltrials.gov as #NCT01884441).Methods:R/R cHL patients after first‐line chemotherapy were eligible. The primary endpoint was CR after four cycles of BEGEV. Secondary endpoints were: ORR, stem cell mobilization, toxicity, progression‐free survival (PFS) and overall survival (OS). The BEGEV regimen consisted of Bendamustine (90 mg/sqm, days 2–3), Gemcitabine (800 mg/sqm, day 1 and 4) and Vinorelbine (25 mg/sqm, day 1) every three weeks for a total of 4 courses. Patients achieving CR or partial remission (PR) after completion of BEGEV were autografted.Results:Fifty‐nine consecutive patients with relapsed (46%) or primary refractory (54%) cHL were enrolled. After BEGEV completion, 44 (75%) patients achieved CR and 5 (8%) PR for an ORR of 83%. In univariate analysis, the only factor which resulted associated with a different probability to reach CR before ASCT was disease status at study entry, with CR being achieved by 84% of relapsed patients and 59% of refractory patients (P = 0.031). With a median follow‐up of 5 years (range, 3.4–79), the overall patient population (n = 59) has an OS of 78% and a PFS of 61%, respectively, without significant difference between relapsed and refractory patients. Of the 49 BEGEV responders, 43 (73% by intention‐to‐treat) proceeded to ASCT and among them, 33 are in continuous CR, 7 relapsed and 3 died [pneumonia (n = 1), infection (n = 1) and multi‐organ failure (n = 1)]. The remaining six patients did not proceed to ASCT due to mobilization failure (n = 2), physician decision (n = 2), early relapse (n = 1), patient refusal (n = 1). Of the 33 patients in CR after ASCT, 15 had primary chemorefractory disease and received ASCT while in PR (n = 3) or CR (n = 12). Relapse occurred after a median of 6.2 months (range 4.8–28) from ASCT with only two patients relapsing beyond 12 months. Patients who relapsed after transplant could be rescued by Brentuximab Vedotin and subsequent allogeneic SCT. For autografted patients, the 5‐yr OS and PFS are 91% and 77%, respectively, without significant difference between patients with relapsed or primary refractory disease (Figure 1). With extended follow‐up, no patient experienced secondary leukemia or myelodysplasia.Summary/Conclusion:With extended follow‐up, the BEGEV regimen is a highly effective and safe salvage regimen allowing a high percentage of patients (73% by ITT) to proceed to ASCT. The salvage program, i.e., BEGEV followed by ASCT, represents a chemotherapy‐based curative strategy for nearly 60% of R/R cHL. However, about 30% of R/R cHL patients progress before BEGEV completion or after ASCT and represent an unmet medical need requiring further development of the BEGEV/ASCT program in combination with anti‐PD‐1 inhibitors used either during the induction phase with BEGEV or as consolidation in the post‐ASCT setting.image