Pharmacological management of chronic lymphocytic leukemia: current and emerging therapies

Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), characterized by its monoclonal lymphoproliferative nature, is an indolent but incurable malignancy. The treatment landscape of CLL/SLL has drastically transformed in the last decade since the introduction of targeted therapy and immune-effector T-cell therapy. The paradigm shift from chemoimmunotherapy to targeted and cellular therapies was largely driven by improved efficacy and safety. With the success of targeted therapies, novel agents and combinations are rapidly emerging on the horizon.

In this review, we will summarize clinical evidence supporting current and emerging therapies with emphasis on investigational therapies and novel combinations of commercial agents. Clinical trials were identified via clinicaltrials.gov, and a PubMed literature search was last performed in June 2024.

With the availability of more effective and better-tolerated treatments for CLL/SLL, the role of early intervention should be further investigated due to its potential to alter disease course, delay progression, and improve overall survival rates. With many highly effective agents and combinations expected to become commercially available, attention to safety profiles and careful selection of patients for each treatment will be critical, with consideration of comorbidities, logistical issues, and financial burden of treatment.