Chemoimmunotherapy with brentuximab vedotin combined with ifosfamide, gemcitabine, and vinorelbine is highly active in relapsed or refractory classical Hodgkin lymphoma

Abstract

Salvage therapy followed by autologous hematopoietic stem cell transplantation (HCT) can be curative in relapsed/ refractory classical Hodgkin lymphoma (cHL) [1]. Complete response (CR) prior to HCT, particularly complete metabolic response (CMR) indicated by a negative positron emission tomography/computed tomography (PET/CT) scan, is highly prognostic of post-transplant outcome [2, 3]. Thus optimization of disease status prior to HCT is highly desirable. There is no gold standard salvage in R/R cHL prior to HCT, and the choice of regimen depends on the physicians’ experience and preference. Brentuximab vedotin (Bv) has demonstrated excellent activity in cHL. Recent reports have combined Bv with standard salvage or with PD-1 inhibitor therapy with higher responses than conventional chemotherapy alone [4–6]. Our aim from this analysis is to examine the efficacy of Bv incorporated within the gemcitabine salvage regimen ifosfamide, gemcitabine, and vinorelbine (IGEV-Bv). After institutional review board (IRB) approval, patients’ ≥ 14 years of age with relapsed or refractory cHL who received IGEV-Bv at our institution between 2013 and 2017 were identified, and all records were retrospectively extracted. Patients were eligible if they had histologically proven evidence of disease and those who achieved a partial metabolic response (PMR) or better to salvage therapy proceeded to HCT [7]. Patients received IGEV as first or subsequent salvage (FS or SS), as previously described [8]. Bv was administered at a dose of 1.8 mg/kg body weight on day 1 of each 3-week IGEV course. A minimum of two cycles of salvage were administered to all patients, and those who did not attain at least a PMR status following two cycles of salvage were switched to an alternate non-cross resistant regimen. All analyzed patients underwent PET/CT staging following one or two cycles of IGEV-Bv to assess response. All studies were performed on GE 710 discovery TF system. Standardized uptake value of the liver and mediastinum is noted, and update was classified per Deauville criteria as ≤ liver uptake or ≤mediastinal blood pool [9]. Patients with uptake ≤ liver (i.e., Deauville 3) were deemed to have CMR. Patients received BEAM (carmustine, etoposide, cytarabine, and melphalan) as conditioning followed by autologous stem cell rescue. All patients were hospitalized during conditioning therapy and until platelet and neutrophil engraftment. Overall survival (OS) was calculated from the date of stem cell infusion until the date of death of any cause or last documented follow-up. Progression-free survival (PFS) was calculated from the date of stem cell infusion until death of any cause or evidence of disease progression or relapse. Baseline patient, disease, and treatment-related variables were reported using descriptive statistics (counts, medians, and percentages). Probability of OS and PFS was computed using the Kaplan–Meier method. Group comparisons were made using the log-rank test. Statistical analyses were performed using JMP Pro Version 11 (SAS Institute, Cary, NC, USA) software and EZR on R commander. A total of 28 patients met the eligibility criteria and were included in this analysis. The median age was 25 (15–49) * Moussab Damlaj [email protected]