The safety of available chemo-free treatments for mantle cell lymphoma

ABSTRACT

Introduction

Conventional treatment for mantle cell lymphoma (MCL) patients includes regimens combining rituximab with other cytotoxic drugs, followed or not by consolidation with autologous stem cell transplantation and rituximab maintenance. However, older, unfit, and relapsed/refractory patients are often ineligible for intense treatment. Currently, available new targeted treatment options seem to offer hope in this group of patients.

Areas covered

This article reviews the safety profiles of new therapeutic chemotherapy-free options for MCL patients. Publications in English from 2010 through June 2020 were surveyed on the MEDLINE database for articles. Proceedings of the American Society of Hematology during the last 5 years were also included.

Expert opinion

MCL is a clinically heterogenous disease predominantly affecting elderly patients. Its variable clinical course requires personalization and individualization of treatment to achieve optimal survival and acceptable safety profiles, especially in poor prognosis patients. Results of clinical trials performed in the past decade indicated that novel drugs used as a single agent or as part of a conventional chemotherapeutic treatment offer promise in minimalizing the relapse rate for MCL and may allow more effective and safer treatment options by reducing the risk of adverse events, especially cytopenias and infections.

KEYWORDS:

• Acalabrutinib
• bortezomib
• clinical efficacy
• ibrutinib
• mantle cell lymphoma
• safety profile
• veneotoclax
• zanubrutinib

Article highlights

• Although front-line therapy of MCL is usually based on classical chemotherapy combined with anti-CD20 antibody according to the patient’s performance status and comorbidities, there is a shift towards chemotherapy-free regimens, especially in relapsed/refractory patients.

• Currently approved BTK or BCL-2 inhibitors, immunomodulatory drugs, and bortezomib used alone or in combination with other agents display high efficacy and favorable toxicity profile with usually mild and manageable undesirable effects.

• The toxicity profile, adherence, and rates of discontinuation for reasons other than progression of novel targeted drugs differ from those of standard regimens.

• Adverse events associated with BTK inhibitors include increased frequency and severity of arrhythmia, AF in particular, and bleeding risk.

• Immune complications associated with PI3K inhibitors particularly idelalisib include colitis, hepatitis, and pneumonitis.

• Tumor lysis syndrome is a rare but life-threatening complication most commonly associated with venetoclax.

This box summarizes the key points contained in the article.

Acknowledgments

The authors would like to thank Mr. Edward Lowczowski for his help in preparing the English version of this manuscript.

Author contributions

A Korycka-Wolowiec, D Wolowiec, and T Robak examined the available data and wrote the review. All authors reviewed and revised the manuscript and provided their approval of the final version of the manuscript. All authors agree to be accountable for all aspects of the work.

Declaration of interest

A Korycka-Wolowiec and D Wolowiec are recipients of research grants from AbbVie. D Wolowiec has received travel grants from Janssen. T Robak has received honoraria and has had consultancy/advisory roles for AbbVie and Janssen; and has received research funding from AbbVie, Janssen, Acerta and Biogen. 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. 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

The study was supported in part by grant funding from the Medical University of Lodz, Poland: No. 503/1-093-01/503-11-004.