Minimizing and managing treatment-associated complications in patients with chronic lymphocytic leukemia

ABSTRACT

Introduction: During recent years, therapy in chronic lymphocytic leukemia (CLL) has changed dramatically. The introduction of small molecule inhibitors has shown remarkable clinical efficacy in both previously untreated and relapsed CLL patients. However, these therapies are associated with an increased risk of specific adverse events. Selection of the best therapeutic approach for patients with CLL should be based on an assessment of general condition, comorbidities, and most importantly, the individual risk of serious side effects.

Areas covered: The review presents available data about the occurrence, prophylaxis and management of the most common and clinically most relevant adverse events associated with novel therapy in CLL.

Expert opinion: The incorporation of novel drugs, such as B-cell receptor inhibitors and venetoclax, a selective inhibitor of B-cell lymphoma, influences the CLL management paradigm. An individualized approach to CLL is now possible with targeted therapies. The appropriate and optimal use of current therapies requires a precise understanding of their mechanisms of action, efficacy and adverse effect profiles. A fuller understanding of the prophylaxis and management of specific adverse events stemming from CLL therapy could minimize its associated morbidity and mortality. Next-generation agents with improved efficacy and better safety profiles will further advance outcomes for patients with CLL.

KEYWORDS:

• Chronic lymphocytic leukemia
• adverse events
• infections
• tumor lysis syndrome
• atrial fibrillation
• ibrutinib
• idelalisib
• venetoclax

Article highlights

• The use of new targeted drugs is associated with a unique profile of side effects which require an optimization of current approach to prophylaxis and supportive treatment.

• The proper use of current therapies in CLL patients should take into account their precise mechanisms of action, efficacy, and adverse event profiles.

• Patients with CLL, particularly those undergoing antileukemic therapy, have a high risk of infections, including opportunistic infections.

• Active monitoring and proper prophylaxis in patients with CLL can decrease the risk of serious infections and their complications.

• New targeted therapies, particularly venetoclax, increase the risk of TLS. Risk assessment, dose escalation and careful observation for TLS, together with proper prophylaxis, is recommended.

• Most drugs used in CLL can induce cytopaenia,most commonly neutropenia. In the case of severe neutropenia, temporary growth factor support can be considered.

• A wide variety of agents used in the treatment ofCLL may cause hepatic injury via several mechanisms. Therapy with idelalisib is associated with a higher risk of hepatotoxicity,probably due tothe adaptive immune response elicited by the inhibition of PI3Kδ in regulatory T cells.

• Therapy with BTK inhibitors is associated with an increased risk of bleeding, particularly when used with ibrutinib. Concurrent use of ibrutinib and anticoagulants is not recommended.

• Diarrhea is frequently reported in CLL patients treated with ibrutinib and idelalisib and can eventually lead to drug dose reduction and/or discontinuation of therapy. If it is unresolved after 48 hours and infection is excluded, steroids should be initiated.

• Patients treated with idelalisib who develop non-infectious pneumonitis should be treated with high dose corticosteroids.

• In patients treated with ibrutinib, an increased rate of AFis observed. However, a previous diagnosis of AF or other cardiac arrhythmia is not a contraindication for ibrutinib therapy.

Acknowledgments

We thank Edward Lowczowski from the Medical University of Lodz for editorial assistance.

Declaration of interest

T Robak has received research support from Hoffman-La Roche Rigel, Jansse, Abbvie, Gilead, Beigene and Acert; travel grant from Hoffman-LA Roche and has participated on advisory boards for Janssen, Abbvie, Gilead, Beigene, Amgenn and Hoffman-La Roche. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was funded by the Medical University of Lodz, Poland [Grant No.503/1-093-01/503-11-004-18].