New and emerging Bruton tyrosine kinase inhibitors for treating mantle cell lymphoma – where do they fit in?

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin’s lymphomas that is generally classified as an aggressive lymphoma requiring front-line chemo-immunotherapy with stem cell rescue. Despite effective treatment, many patients relapse or are refractory to front-line therapy. In addition, these patients may also develop drug resistance requiring novel modalities for subsequent lines. Bruton’s tyrosine kinase inhibitors have demonstrated a well-tolerated safety and efficacy profile across several B-cell malignancies. Ibrutinib, acalabrutinib, and zanubrutinib are FDA-approved as treatment options for patients with Mantle cell lymphoma following one prior line of therapy. Various factors should be considered which include the adverse event profile of these agents and ability to adhere to therapy. In this article, we review the role of Bruton’s tyrosine kinase inhibitors for the management of Mantle cell lymphoma and review the clinical pharmacology, pharmacokinetics, safety and efficacy, and future directions.

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Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma

Current Oncology ◽

10.3747/co.26.4345 ◽

2019 ◽

Vol 26 (2) ◽

Cited By ~ 18

Author(s):

C. Owen ◽

N. L. Berinstein ◽

A. Christofides ◽

L. H. Sehn

Keyword(s):

Tyrosine Kinase ◽

Mantle Cell Lymphoma ◽

First Generation ◽

Kinase Inhibitors ◽

Cell Lymphoma ◽

Comparable Efficacy ◽

Non Hodgkin Lymphoma ◽

Mantle Cell ◽

Bruton Tyrosine Kinase ◽

Btk Inhibitors

Mantle cell lymphoma (mcl) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (r/r) disease have a very poor prognosis. The Bruton tyrosine kinase (btk) inhibitor ibrutinib has proven to be an effective agent for patients with r/r mcl. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with r/r mcl are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with r/r mcl.

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Role of Tyrosine Kinase Inhibitors in Indolent and Other Mature B-Cell Neoplasms

Biomarker Insights ◽

10.4137/bmi.s22434 ◽

2015 ◽

Vol 10s3 ◽

pp. BMI.S22434

Author(s):

Nadine Kutsch ◽

Reinhard Marks ◽

Richard Ratei ◽

Thomas K. Held ◽

Martin Schmidt-Hieber

Keyword(s):

Tyrosine Kinase ◽

B Cell ◽

Mantle Cell Lymphoma ◽

Tyrosine Kinase Inhibitors ◽

Tyrosine Kinases ◽

Kinase Inhibitors ◽

Cell Lymphoma ◽

Chemotherapeutic Agents ◽

Mantle Cell

Targeting tyrosine kinases represents a highly specific treatment approach for different malignancies. This also includes non-Hodgkin lymphoma since it is well known that these enzymes are frequently involved in the lymphomagenesis. Hereby, tyrosine kinases might either be dysregulated intrinsically or be activated within signal transduction pathways leading to tumor survival and growth. Among others, Bruton's tyrosine kinase (Btk) is of particular interest as a potential therapeutic target. Btk is stimulated by B-cell receptor signaling and activates different transcription factors such as nuclear factor KB. The Btk inhibitor ibrutinib has been approved for the treatment of chronic lymphocytic leukemia and mantle-cell lymphoma recently. Numerous clinical trials evaluating this agent in different combinations (eg, with rituximab or classical chemotherapeutic agents) as a treatment option for aggressive and indolent lymphoma are under way. Here, we summarize the role of tyrosine kinase inhibitors in the treatment of indolent and other non-Hodgkin lymphomas (eg, mantle-cell lymphoma).

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