Magic pills: new oral drugs to treat chronic lymphocytic leukemia

ABSTRACT

Introduction: A deeper understanding of chronic lymphocytic leukemia (CLL) biology has led to the identification of new promising therapeutic targets. Different classes of molecules are currently under investigation and novel oral drugs have recently been approved or are in a late stage of clinical development.

Areas covered: We present biological data illustrating the heterogeneous mechanisms of action of new oral drugs in CLL. Moreover, we provide clinical data from phase I to III studies, and discuss efficacy and side effects profile of these new therapies. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings.

Expert opinion: Novel oral drugs represent a valuable alternative to chemo-immunotherapy for patients with CLL, especially when high-risk disease features are present and when age or comorbidities preclude the use of standard treatments. Based on data from ongoing clinical trials, the indications of already approved agents will most likely be expanded and new options will soon be available. Moreover, treatment combinations will broaden the therapeutic armamentarium of physicians treating CLL. The availability of multiple choices is of benefit for patients with CLL, but also represents a challenge for the need of choosing the right drug for each patient.

KEYWORDS:

• Chronic lymphocytic leukemia
• ibrutinib
• idelalisib
• new drugs
• target therapy
• venetoclax

Article highlights

• Novel oral targeted drugs have been recently approved for the treatment of patients with CLL, and more compounds, which are now in advanced stage of development, will soon be available.

• The new chemo-free options are a game changer, particularly for CLL patients with high-risk disease (del(17p)/TP53 mutated) and for elderly/unfit populations, and based on their high efficacy a broadening of current indications is anticipated.

• The oral formulation and the need for continuous administration raise new issues in CLL management, such as compliance and costs, which will need to be addressed.

• A longer follow-up will help to better characterize the spectrum of side effects of novel oral agents, and results from ongoing studies will clarify whether combination therapies may eventually result in deeper and more durable responses.

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Declaration of interest

C Vitale is a recipient of a fellowship from the Associazione Italiana Controle leucemie-Linfomi e mieloma and has received honoraria from Gilead. V Griggo is a recipient of a fellowship ‘Anna Nappa’ from Associazione Italiana per la Ricerca sul Cancro. M Boccadoro has received honoraria and research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, AbbVie, Brisol-Myers Squibb and Mundipharma. M Coscia has received honoraria from Roche, Gilead, Janssen and Mundipharma; is on the advisory board from Roche and has recieved research funding from Karyopharm 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.

Additional information

Funding

This paper is not funded