Brentuximab Vedotin in First Refractory/Relapsed Classical Hodgkin Lymphoma Patients Treated By Chemotherapy (ICE) before Autologous Transplantation. Final Analysis of Phase II Study

Introduction: About 10-15% of patients with localized and 25-30% with disseminated classical HL failed to respond or relapse after primary conventional treatment. For the youngest, autologous stem cell transplantation (ASCT) is a standard of care after salvage chemotherapy leading to an increased disease free survival (DFS). With this strategy 50 to 70% of patients with chemo sensitive disease become eligible for ASCT. As the disease status before ASCT appears to be the most important factor predicting outcome, second line chemotherapy has to be more efficient. Brentuximab-Vedotin (BV) has shown significant activity (SG035-0003) in patients with relapsed or refractory HL. Therefore, it seems logical to use BV in patients treated with ICE before ASCT in order to induce a better Complete Metabolic Response (CMR) rate evaluated by FDG-PET (Deauville score 1-3). Methods: BV was added to ICE in a phase I/II trial chemotherapy trial sponsored by LYSARC with a financial support by Millenium. The optimal dose of BV (1.8 mg/kg) with ICE (3 cycles) was established in the phase I of the study (10 patients). In the second part of the study (phase II), efficacy and toxicity of the Recommended Phase II Dose (RP2D) was assessed. Patients received 2 cycles of BV ICE before evaluation and only CMR received the third course, than an injection of brentuximab alone before ASCT. Primary endpoint was CMR after 2 cycles of treatment. Results: Final analysis was performed in 42 patients for toxicity and 39 patients for the efficacy set. Baseline characteristics were median age: 30 years (range: 18-65), Sex ratio (M/F): 27/15, nodular sclerosis histology in 83%, stage III/IV in 67 % and status of the disease: 12 refractory patients and 30 relapsed patients with a median time to first relapse of 19 months (9-159). First-line treatment was escBEACOPP (n =21) ABVD (n= 17) OEPA/copdac (n= 2) PVAB (n=1) CHOP (n =1). All patients received the two first cycles, 78.6 % the third cycle and 71 % the brentuximab alone without modification of doses but with delay of at least one cycle in 45 %. Grade 3-4 adverse events were encountered in 35 patients (83%) mainly due to hematologic toxicity (71%) followed by infection (21%) and gastro-intestinal disorders (10%). No neuropathy and no toxic death were observed. Most patients (69.2%, n=27) had CMR, followed by PMR (25.6%, n=10). Among the 39 patients, three patients (7.7%) had progressive disease during treatment phase. Leukaphereses were performed in 31 patients (79%) median collected D34+ cells was 7.2 (106/kg) and 20 patients out of the 25 with CMR underwent ASCT. Thirteen patients relapsed mainly during follow-up (10) and no death was observed without progression. The median PFS was not reach and the one-year-PFS was 69% [95% CI: 53%-81%]. Conclusion: Two cycles of BV in R/R HL patients who are treated by ICE chemotherapy allows a CMR in 69.2 % of evaluable patients with sufficient harvest for an ASCT. These results are comparable to other salvage chemotherapies only after two cycles with acceptable toxicities. Disclosures Stamatoullas: Takeda: Consultancy; Celgene: Honoraria. Quittet:Novartis: Honoraria, Speakers Bureau. Morschhauser:F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees. Ribrag:Epizyme: Consultancy, Research Funding; ArgenX: Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses ; MSD: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses . Brice:Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria.