Venetoclax, Obinutuzumab and Atezolizumab (PD-L1 Checkpoint Inhibitor) for First-Line Treatment for Patients with Chronic Lymphocytic Leukemia (CLL)

Background: Dysfunction of T cells, NK cells and other immune subsets is common in patients (pts) with CLL. Venetoclax (VEN), a BCL-2 inhibitor and obinutuzumab (OBIN), a CD20 monoclonal antibody (mAb) are approved for pts with CLL (Fischer, NEJM 2019). Atezolizumab, a PD-L1 checkpoint inhibitor (CPI), is approved for melanoma, lung cancer and other solid tumors. Preclinical studies showed synergy of VEN and CD20 mAb with CPI (Kohlhapp, Cancer Discovery 2021; Westin, Lancet Oncology 2014). Clinical studies showed activity of PD1 inhibition in pts with Richter's transformation, but not CLL (Ding, Blood 2017; Jain, ASH 2018). To our knowledge, no prior study has evaluated PD-L1 inhibition in pts with CLL, nor combined CPI, VEN and OBIN. We hypothesized that combined VEN, OBIN and atezolizumab will be synergistic.