BRENTUXIMAB VEDOTIN SALVAGE FOLLOWED BY CONSOLIDATION POST AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN HIGH RISK RELAPSED REFRACTORY HODGKIN LYMPHOMA

Abstract

Introduction: Brentuximab vedotin (Bv) improves PFS post autologous HCT in high risk relapsed/refractory classical Hodgkin Lymphoma (r/r cHL). Furthermore, chemoimmunotherapy salvage with Bv results in a higher rate of complete metabolic response (CMR) compared with chemotherapy alone as shown by multiple groups. Attainment of such CMR status prior to HCT is highly predictive of prolonged remissions. Aim: To examine the outcome of Bv containing salvage followed by consolidation in high risk r/r cHL. Primary endpoint was overall response rate (ORR) including rate of CMR. Secondary endpoint was 2-year PFS and overall survival (OS). Methods: Pts with high risk r/r cHL whom were candidates for curative HCT were identified and all records were retrieved retrospectively after IRB approval. High risk r/r cHL was defined as patients with primary refractory disease, relapse within 12 months of front line therapy or relapse with extranodal disease. Patients received Bv with salvage at 1.8 mg/kg on day 1 of each cycle. Post-HCT Bv consolidation was given starting day 30-45 at 1.8 mg/kg every 3 weeks for up to 16 cycles. Response assessment was done in accordance with the Lugano criteria including the definition of CMR as deauville score ≤ 3. OS and PFS were computed using Kaplan-Meir method with log ranks test. Results: A total of 20 patients were identified and all records retrospectively collected. Baseline characteristics were as follows; 11 (55%) male with median age at HCT of 22 years. 12 (60%) had refractory disease with median time to relapse following front line therapy of 3.7 months. Bv was given with IGEV in 14 (70%), ESHAP in 4 (20%) and Bendamustine in 2 (10%). The ORR was 100% and all patients had evidence of partial response or better. Furthermore,14 (70%) of patients achieved CMR status pre-HCT. A total of 19 patients were collected during salvage with GCSF while the remaining patient was mobilized with GCSF alone. Median CD34 x106/kg collected was 12.75 (2.51-42.5) and the median time to ANC and platelet engraftment was 12 (9-15) and 16 (11-20) days, respectively. Post HCT, all patients received Bv consolidation with a median number of doses of 12 (3-16). Observed adverse events on Bv consolidation were; grade 3 neutropenia in 9 (45%) requiring GCSF support in all and dose reduction in 6 (30%), neuropathy grades 1-3 in 2 patients (15%), 3 (15%) and 1 (5%) leading to early discontinuation of planned consolidation in 4 (20%). Neuropathy resolved or improved in all cases. A total of 2 patients relapsed, both while on Bv consolidation. Median follow up was 15.4 months (3.8-56) with estimated 2-year PFS and OS of 83% and 95%, respectively as shown in table 2 and figure 1 A-B. Keywords: brentuximab vedotin; classical Hodgkin lymphoma (cHL); Deauville's criteria.