CELL INTELLIGENCE · 肿瘤细胞治疗研究

Richter transformation (RT) is a rare albeit devastating complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). RT is defined as an aggressive lymphoma, typically diffuse large B-cell lymphoma, in the setting of CLL. A clonal relationship to the preceding CLL clone is detected in the majority of RT cases and confers more aggressive clinicopathologic kinetics, resistance to standard chemoimmunotherapy regimens, and inferior survival. Taken together, these considerations precipitate a significant unmet need for novel therapeutic strategies that improve the outcomes of patients with RT. Through this review, we will explore current data on emerging regimens targeting BTK, BCL-2, CD79, CD20, PI3K, and PD-1-both as single agents and as combination therapies with or without concurrent chemoimmunotherapy. Furthermore, we will review the role of bispecific T-cell engagers, anti-CD19 chimeric antigen receptor T-cell therapies, and hematopoietic stem cell transplantation in RT. To guide therapeutic decision-making, we will outline an algorithmic approach to the management of RT, with particular emphasis on prioritization of clinical trial enrollment and utilization of an ever-evolving array of novel therapies.