An in-depth evaluation of acalabrutinib for the treatment of mantle-cell lymphoma

ABSTRACT

Introduction: Regimens involving intensive immuno-chemotherapy, followed by high-dose therapy and autologous stem cell transplant represent the standard treatment for younger fit patients with mantle cell lymphoma (MCL). Targeted approaches (i.e. ibrutinib, bortezomib, and lenalidomide) represent the backbone of therapy for relapsed cases.

Areas covered: Acalabrutinib is a novel small molecule with a butynamide moiety specifically designed to irreversibly inhibit Bruton tyrosine kinase (BTK), which is more potent and selective than ibrutinib. Relevant publications have been identified through literature searches using the terms ‘mantle cell lymphoma’ and ‘acalabrutinib’.

Expert opinion: Acalabrutinib has been approved for the treatment of relapsed/refractory (RR) MCL patients. To date, clinical trials have reported some adverse effects such as cardiac toxicity or atrial fibrillation. Acalabrutinib in combination with other drugs, either in chemo-containing or chemo-free schedules, represent a valid option for MCL. However, none of the treatment schedules containing BTK inhibitors have been shown to be curative in MCL. Acalabrutinib may ultimately represent an option for patients who are ‘fit’ and exhibit well-controlled disease, which often characterizes only a limited ‘niche’ among MCL patients.

KEYWORDS:

• Acalabrutinib
• MCL
• therapy
• BTK

Article highlights

• MCL is a clinically heterogeneous disease characterized by a relatively short survival in cases with aggressive disease.

• Upfront chemoimmunotherapy consisting of cytarabine-containing induction followed by consolidation with high-dose chemotherapy and subsequent autologous-SCT has not overcome poor outcomes.

• Acalabrutinib is a highly selective BTK inhibitor approved for the treatment of RR-MCL patients, with a more favorable toxicity profile compared to ibrutinib.

• Currently, overcoming resistance mechanisms to BTK inhibitors remains the upcoming challenge.

• Combination therapy of acalabrutinib with other agents either in the presence of chemotherapeutics or in chemo-free arrangements might represent an option for MCL.

• A newer generation of BTK inhibitors is currently being evaluated.

Declaration of interest

The authors have no 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

One referee has received research funding for work on BTK inhibitors and has served on advisory boards for AstraZeneca, Acerta, Celtrion, and Merck & Co. Another referee was a co-author on a phase II study on acalabrutinib in MCL. A third referee declares that they have served on the advisory board of AstraZeneca. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

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Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This manuscript was not funded.