Current therapies for chronic lymphocytic leukemia: risk and prophylaxis strategies for secondary/opportunistic infections

ABSTRACT

Introduction

Currently, the implementation of new therapeutic options for treatment of chronic lymphocytic leukemia (CLL) considerably improved the outcome of this disease. However, patients affected by CLL are at higher risk for infections, due to the state of immunosuppression related to hematologic disease and therapies. Consequently, anti-infective prophylaxis should be properly managed, according to risk factors for opportunistic infection, related to antineoplastic drugs and characteristics of patients.

Areas covered

This review aims to summarize current knowledge on secondary/opportunistic infections during CLL treatment, including chemo-immunotherapies, Bruton Tyrosine Kinase inhibitors, idelalisib and venetoclax. In addition, possible schemes of prophylaxis are provided.

Expert opinion

The establishment of a multidisciplinary team including hematologist and infectious diseases specialist is pivotal for the best management of anti-infective prophylaxis and prevention of new onset infections.

KEYWORDS:

• Chronic lymphocytic leukemia
• targeted therapies
• screening, viral hepatitis
• Latent tuberculosis infection
• herpetic infection
• Pneumocystis jirovecii pneumonia
• COVID-19
• prophylaxis

Article highlights

• Patients affected from CLL are exposed to high risk of reactivation of latent infections and occurrence of opportunistic infections, with an increased risk of morbidity and mortality: every patient should be screened for latent infection at time of CLL diagnosis.

• Treatment with Direct Antiviral Agents should be encouraged in all patients affected by chronic HCV infection. Drug-drug interaction with antineoplastic comedications should be carefully monitored.

• Antiviral prophylaxis against chronic HBV infection is mandatory during anti-CD20 monoclonal antibodies.

• Anti-tubercular prophylaxis is suggested when a positive Quantiferon test is obtained, since the prolonged life expectancy and long-term hematologic treatment could increase reactivation the risk of LTBI. Drug-drug interactions should be strictly monitored.

• Prophylaxis with acyclovir against HSV/VZV reactivation is usually recommended.

• Idelalisib is associated with higher risk of CMV reactivation; closer clinical and laboratoristic monitoring is required.

• Risk of opportunistic pneumonia caused by Pneumocystis jirovecii should be considered in all subjects with deep lymphopenia, particularly of CD4+ cells.

• Patients affected by CLL are at high risk for severe COVID-19; preventive measures, including vaccination and pre-exposure prophylaxis with SARS-CoV-2–neutralizing monoclonal antibodies according to circulating variants of concern (e.g. tixagevimab and cilgavimab), are needed.

Additional information

Funding

This paper was not funded.