Richter transformation: biological insights, diagnostic challenges and emerging therapies.

PURPOSE OF REVIEW: this review aims to underscore the significance of the growing number of advances related to Richter transformation (RT), an aggressive form of lymphoma arising in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

RECENT FINDINGS: The development of sequencing analytic tools and single-cell approaches has overcome the major challenge of cellular admixture in RT, enabling a deeper understanding of the genetic alterations driving transformation from CLL to RT. These techniques have also made it possible to detect RT clones long before clinical onset. In parallel, novel targeted therapies for CLL and immunotherapeutic strategies for lymphomas are offering renewed hope. Recent phase 2 studies notably support the potential role of immune checkpoint inhibitors and bispecific T-cell engagers in RT, while experience with chimeric antigen receptor T-cell therapies continues to grow, raising hopes for improved outcomes in this historically difficult-to-treat condition.

SUMMARY: recent research is focusing on better understanding the transformation process, improving the early detection of RT, and developing novel targeted and immunotherapy treatments and combinations for patients with RT.