Richter Transformation and Emerging Therapies in CLL

Dr. Jennifer J. Huang discusses when to suspect Richter transformation in patients with chronic lymphocytic leukemia (CLL), highlighting concerning symptoms such as fevers, drenching night sweats, and significant fatigue that may raise suspicion for an aggressive B-cell lymphoma. She explains the role of imaging to identify highly FDG-avid lesions and guide biopsy of the most metabolically active site to evaluate for transformation. Dr. Mazyar Shadman reinforces the importance of investigating Richter transformation when the clinical presentation raises concern. The discussion then shifts to clinical trials and emerging therapies for CLL, including BTK degraders, which target the BTK protein for degradation rather than simply inhibiting its activity. Dr. Huang also discusses the investigational next-generation BCL-2 inhibitor sonrotoclax, which may offer a lower risk of tumor lysis syndrome and potentially allow faster dose escalation. The experts additionally highlight investigational bispecific antibodies and emphasize the continued importance of clinical trial participation across treatment settings, particularly for patients whose disease has progressed after available treatment options.