A phase I/II b (randomized controlled) study of atezolizumab combined to BEGEV regimen as first salvage treatment in patients with relapsed or refractory Hodgkin’s lymphoma candidate to autologous stem–cell transplantation

The complete response rate (CRR) achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). 
In recent years, our group has developed a pre-transplant salvage chemotherapy regimen called BEGEV, composed of bendamustine, gemcitabine, and vinorelbine. This regimen, administered before ASCT, has proven to be an optimal treatment, capable of inducing a complete response rate of 75%, with a 5-year progression-free survival (PFS) of 59%. 
This CR rate is significantly higher than that obtained with various other second-line salvage regimens. 
Recently, the critical role of the immune system in controlling tumor progression has been widely demonstrated. Programmed cell death protein 1 (PD-1) is a key immune checkpoint molecule expressed on T cells, involved in the depletion of CD4+ T cells and in mechanisms through which tumors evade immune surveillance. 
Checkpoint inhibitors (CPIs) targeting PD-1, such as Nivolumab and Pembrolizumab, have shown remarkable efficacy by inducing high remission rates with manageable toxicity, and they have been approved for clinical use in R/R cHL, both before and after transplant. 
These findings support the rationale for fully blocking the PD-1 / Programmed death-ligand 1 (PD-L1) axis as a therapeutic strategy in patients with R/R cHL. 
Atezolizumab is a human monoclonal IgG1 antibody targeting PD-L1, inhibiting its interaction with PD-1 and B7-1. 
Several ongoing studies are evaluating combination therapies involving Atezolizumab with either standard chemotherapy or novel biologic agents in patients with advanced/metastatic solid tumors as well as hematologic malignancies. 
The rationale behind combining immune checkpoint inhibitors with conventional chemotherapy is to enhance antitumor activity and consolidate chemotherapy-induced responses without significantly increasing toxicity. 

For these reasons, and with the goal of increasing the number of patients achieving complete remission (CR) prior to ASCT, combining BEGEV with Atezolizumab is hypothesized to be a valid and rational approach for patients with relapsed or refractory disease, where salvage therapy should be followed by high-dose therapy and autologous stem cell transplantation.