Towards Identifying Which CLL Patients with Richter Transformation Respond to Immune Checkpoint Inhibitor Therapy

Pre-existing cytotoxic activity in CD8⁺ and CD4⁺ T cells is a defining feature of Richter transformation in CLL and is associated with increased responsiveness to anti–PD-1 therapy. While immune checkpoint inhibitors show clinical activity, the tumor microenvironmental determinants of response remain incompletely defined. Data presented by Johan Gustafsson, Postdoc at Broad Institute of MIT and Harvard, Cambridge, USA, at ASH 2025 indicate that preserved splenic architecture, immune cell aggregates, and enhanced cytotoxic T-cell function are critical for effective immune checkpoint blockade.