Ibrutinib for the treatment of mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin’s lymphoma. It can follow a heterogeneous clinical course but generally patients relapse early after standard immunochemotherapy regimens and develop resistance to subsequent therapies. For younger patients, intensive approaches followed by autologous stem cell transplantation offer excellent long-term disease control but with the possible exception of an allogenic stem cell transplant, MCL is an incurable condition. As MCL principally affects older individuals, the majority of patients are not candidates for such intensive approaches. Ibrutinib is an orally active, Bruton’s tyrosine kinase inhibitor. It inhibits signaling pathways downstream of Bruton’s tyrosine kinase that appear critical for the proliferation and survival of MCL. As a single agent it has shown extremely promising activity in relapsed and refractory MCL patients with an excellent side-effect profile. The exact role for ibrutinib in the treatment of MCL is yet to be established; however, it is likely to fundamentally change the way we treat this disease.

Keywords::

• Bruton’s tyrosine kinase inhibitor
• ibrutinib
• mantle cell lymphoma

Financial & competing interests disclosure

S Rule is on the Advisory Board for Pharmacyclics and Johnson & Johnson. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Ibrutinib is a novel small molecule, which is orally active, irreversible inhibitor of Bruton’s tyrosine kinase that binds on the Cys-481.

• It has been granted one of the first approvals through the US FDA’s Breakthrough Therapy Designation Pathway.

• Ibrutinib is approved for use in relapsed/refractory mantle cell lymphoma patients who have had at least one prior therapy.

• The approval was granted following the Phase II trial, which demonstrated excellent single agent efficacy together with very modest toxicity in relapsed/refractory mantle cell patients.

• Ibrutinib’s favorable toxicity profile potentially allows for it to be incorporated into existing chemotherapy regimens without problems.

• There are currently multiple studies ongoing to evaluate ibrutinib in combination with other immunochemotherapies.

• A number of Bruton’s tyrosine kinase inhibitors are in early clinical development and multiple other small molecules with activity in mantle cell lymphoma are emerging.

• Ibrutinib is set to fundamentally change the treatment approach in mantle cell lymphoma.

Notes