Keeping a balance in chronic lymphocytic leukemia (CLL) patients taking ibrutinib: ibrutinib-associated adverse events and their management based on drug interactions

ABSTRACT

Introduction

Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy.

Areas covered

The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism.

Expert opinion

Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.

KEYWORDS:

• Chronic lymphocytic leukemia (CLL)
• ibrutinib
• atrial fibrillation (AF)
• hemorrhage
• invasive fungal infection
• coronavirus disease (COVID-19)
• lymphocytosis
• drug interaction
• dose modification strategy

Article highlights

• Ibrutinib has excellent therapeutic efficacy and well-tolerated toxicity profiles in patients with CLL.

• Adverse events such as atrial fibrillation, hemorrhage, and infection are emerging as significant factors leading to therapy discontinuation in the real-world, even in patients with optimal treatment response.

• In the global pandemic of COVID-19, CLL patients taking ibrutinib may have a benefit of not progressing to severe infection.

• Isolated lymphocytosis is a common phenomenon induced by ibrutinib, and should not be interpreted to imply treatment failure without other clinical evidence of disease progression.

• Drug interactions with CYP3A4 inhibitors can potentially elevate the plasma concentration of ibrutinib.

• To minimize the incidence of adverse events, close inspection of the prescribed medications and education of patients on ibrutinib-associated toxicities is necessary prior to initiating ibrutinib.

• Lowering the dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be a reasonable strategy to alleviate toxicities including prevention of invasive fungal infection risk while maintaining therapeutic efficacy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.