The combination of venetoclax and rituximab for the treatment of patients with recurrent chronic lymphocytic leukemia

ABSTRACT

Introduction

In patients with recurrent chronic lymphocytic leukemia (CLL), treatment with targeted agents such as Bruton tyrosine kinase inhibitors and the Bcl-2 inhibitor venetoclax is rapidly replacing chemo-immunotherapy regimens. Venetoclax has demonstrated efficacy as monotherapy in patients with previously treated CLL and has been evaluated in combination with the anti-CD20 monoclonal antibody rituximab.

Areas covered

This review focuses on the activity and toxicity of the time-limited combination of venetoclax plus rituximab for the treatment of relapsed or refractory CLL, presenting clinical trial results and data from correlative studies, with the aim of highlighting the strengths of this treatment approach and discuss weaknesses and possible areas of improvement. Data from PubMed indexed papers as well as from abstracts presented at major international conferences are included.

Expert opinion

Deep responses with venetoclax-based regimens have been shown to allow time-limited treatment and prolonged remission off-therapy in patients with CLL. The clinical benefit of venetoclax and rituximab over chemo-immunotherapy has been demonstrated in recurrent CLL. Potential advantages of time-limited treatment approaches include avoidance of long-term toxicities, high drug costs, and the selection of resistant subclones.

KEYWORDS:

• Chronic lymphocytic leukemia
• minimal residual disease
• rituximab
• time-limited therapy
• venetoclax

Article highlights

• Patients with recurrent CLL treated with venetoclax plus rituximab achieve high response rates and eradication of minimal residual disease.

• The combination regimen of venetoclax and rituximab has been designed with a fixed duration of two years, representing a paradigm change in the treatment of CLL with targeted agents, which were previously given continuously, until disease progression or unacceptable toxicity.

• The clinical benefit of the combination of venetoclax and rituximab over chemo-immunotherapy (bendamustine and rituximab) has been demonstrated in a phase III randomized clinical study.

Acknowledgments

C.V. received a “Fondazione Pezcoller – Ferruccio ed Elena Bernardi” fellowship, from Pezcoller Foundation in collaboration with SIC (Società Italiana di Cancerologia).

Declaration of interest

C.V. received consultancy fees from Janssen. A.F. participated in an advisory board for Janssen. The authors have no other relevant affiliations or financial involvement to disclose.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded. 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.