On the front line: first choice pharmacotherapeutics for chronic lymphocytic leukemia

ABSTRACT

Introduction: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with a highly variable clinical course. Frontline treatments include cytotoxic chemotherapies, immunotherapies, and small molecule inhibitors. Clinical and molecular factors guide treatment initiation and selection. Over the last decade, refinement of CLL risk stratification tools and growth of the arsenal of effective therapeutics have profoundly improved outcomes. These advances have concurrently increased the complexity of managing the early phases of treatment.

Areas covered: This review describes the factors considered in the determination of first-line treatment of CLL. Areas of emphasis include assessment of patient fitness, disease classification and risk stratification, and the mechanisms, efficacy, and toxicities associated with available pharmacotherapeutics.

Expert opinion: Multiple different treatments may be appropriate for a specific clinical scenario, and selection among them requires discussion of relative risks and benefits. Advances in frontline CLL treatment will continue to shift the treatment paradigm toward prioritizing quality of life alongside survival, limiting treatment and toxicity, and the development of biologically rational synergistic drug combinations and sequences.

KEYWORDS:

• Chronic lymphocytic leukemia
• frontline
• treatment

Article Highlights

• Initiation of frontline therapy for CLL requires consideration of the interplay of clinical, biologic, and psychosocial factors.

• Objective assessment of patient fitness, including through formal geriatric evaluation where appropriate, is essential to optimize treatment selection.

• Though evolution toward a chemotherapy-free paradigm is sought and expected, intravenous cytotoxic drugs remain an important frontline CLL treatment option.

• Ongoing and future research may find that small molecule inhibitors can be safely stopped, such as in cases of negative minimal residual disease.

• Novel agents and rational combination and sequencing of drugs have the potential to shift the goal of frontline CLL pharmacotherapeutics from palliative to curative.

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Declaration of interest

S Graf reports research funding support from AstraZeneca, BeiGene and TG Therapeutics. 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 relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.