ABSTRACT
INTRODUCTION: In recent years, innovative mechanism-based drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia (CLL) and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway and the BCL-2 anti-apoptotic protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, treatment with ibrutinib, idelalisib and venetoclax is associated with unique side effects. Awareness, prevention and the appropriate management of these specific toxicities are of crucial importance for a successful treatment. Areas covered: The purpose of this review is to discuss the most relevant studies on small molecules in CLL, with particular attention to the emerging toxicity profile of these agents and to the factors that should be considered to address the most appropriate treatment approach for each patient. Expert opinion: The increased knowledge on the biology of CLL has translated into the development of targeted agents that are highly effective and produce deep responses. Toxicities potentially associated with these agents should be known for an optimal management of CLL patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Molecular Targeted Therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Decision-Making , Disease Management , Drug Interactions , Fusion Proteins, bcr-abl/antagonists & inhibitors , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Risk Factors , Treatment OutcomeABSTRACT
INTRODUCTION: About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL. The most frequently observed age-related toxicities, fitness assessments, supportive care measures and treatment options for elderly patients and for patients who are deemed unfit will be discussed. Literature search methodology included examination of PubMed index. Expert commentary: During the last decade, different trials focusing on elderly/unfit patients have investigated more tolerable chemoimmunotherapy schedules and, more recently, the activity and safety of chemo-free regimens. Chlorambucil combined with an anti-CD20 monoclonal antibody has shown clinical activity with a relatively good profile of toxicity. The recent introduction of the B-cell receptor antagonists, ibrutinib and idelalisib, and other targeted drugs in development (e.g. venetoclax), is broadening the therapeutic armamentarium of elderly CLL patients.
