Real-World Data of Nivolumab in Classical Hodgkin Lymphoma: Results from the Italian Expanded Access Programme

Introduction: Nivolumab is the first checkpoint inhibitor approved for the treatment of patients (pts) with relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL). In previous studies, agents who target the PD-1 pathway have demonstrated to show substantial and durable response rates, with encouraging survival data and acceptable safety profile in this pts population. The Expanded Access Programme (EAP) provided the opportunity to treat pts before market availability of the drug. The aim of this analysis is to provide information about nivolumab use in a real world setting as well as in pts subgroups usually excluded from clinical trials.

Methods: Nivolumab was made available through the EAP conducted in Italy between July 2015 and December 2016 and treatment was delivered according to a prespecified protocol approved by ethical committees of participating centers. Pts aged ≥10 years, with histologically confirmed cHL who either failed or were not eligible for ASCT and failed brentuximab vedotin, were eligible if they had an ECOG Performance Status ≤2. Patients could have received prior allogenic transplantation if 6 or more months had lapsed since transplant and pts had no history of acute GVHD or extensive chronic GVHD. Nivolumab (3 mg/kg) was administered intravenously every 2 weeks until disease progression or unacceptable toxicity for up to 2 years. Pts included in the analysis received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.

Results: A total of 133 pts were enrolled across 40 Italian sites. Median age was 35 years (range: 15-82), 65% of pts were male and median number of previous lines of therapy was 4 (range 1-9), with 128 pts (96%) who had received prior brentuximab, 73 pts (55%) who had received prior autologous stem cell transplantation (ASCT) and 27 pts (20%) who had received prior allogenic stem cell transplantation (allo-SCT). At first tumor assessment, the objective response rate (ORR) was 68%, with 20 pts (15%) with complete response (CR), 71 (53%) with partial response (PR) and 18 (14%) with stable disease (SD). Among pts with no prior response to brentuximab (n= 74), ORR was 71%. At a median follow-up of 10.6 months (range 1-19), 1-year progression free survival (PFS) and overall survival (OS) were 61.4% and 89.0%, respectively. Overall, 68 pts (51%) discontinued treatment for the following reasons: 21 pts (13%) due to disease progression, 14 pts (10%) due to adverse events, 31 pts (23%) proceeded to transplantation (20 pts were bridged to allo-SCT and 11 pts to ASCT) and 2 pts for other reasons (physician decision). No treatment related deaths have been reported.

Conclusions: To date, this is the largest clinical experience with nivolumab in a real world setting in pts with R/R cHL. Data confirm results from pivotal trial demonstrating that nivolumab is a safe and effective therapy in this pts population, regardless of number and type of prior therapies. Importantly, about one quarter of pts were bridged to transplantation further supporting that PD1-blockade can overcome resistance to prior conventional treatments.