Ibrutinib in B-cell lymphoma: single fighter might be enough?
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Cancer Cell International Open Access
REVIEW
Ibrutinib in B-cell lymphoma: single fighter might be enough? Chao Xue1, Xin Wang1,2,3, Lingyan Zhang3, Qingyuan Qu1, Qian Zhang3 and Yujie Jiang3*
Abstract Background: In recent years, the B cell receptor (BCR) signaling pathway has become a “hot point” because it plays a critical role in B-cell proliferation and function. Bruton’s tyrosine kinase (BTK) is overexpressed in many subtypes of B-cell lymphoma as a downstream kinase in the BCR signaling pathway. Ibrutinib, the first generation of BTK inhibitor, has shown excellent antitumor activity in both indolent and aggressive B-cell lymphoma. Main body: Ibrutinib monotherapy has been confirmed to be effective with a high response rate (RR) and welltolerated in many B-cell lymphoma subgroups. To achieve much deeper and faster remission, combination strategies contained ibrutinib were conducted to evaluate their synergistic anti-tumor effect. Conclusions: For patients with indolent B-cell lymphoma, most of them respond well with ibrutinib monotherapy. Combination strategies contained ibrutinib might be a better choice to achieve deeper and faster remission in the treatment of aggressive subtypes of B-cell lymphoma. Further investigations on the long-term efficacy and safety of the ibrutinib will provide novel strategies for individualized treatment of B-cell lymphoma. Keywords: B-cell lymphoma, B cell receptor (BCR) signaling pathway, Bruton’s tyrosine kinase (BTK), Ibrutinib, Monotherapy Background Among lymphatic malignancies, B-cell lymphoma is the most common type, accounting for 85% of non-Hodgkin lymphoma (NHL). It has been confirmed that the B cell receptor (BCR) signaling pathway, once revealed in 1993, plays an important role in the occurrence and development of B-cell lymphomas [1]. Bruton’s tyrosine kinase (BTK) is a downstream kinase that plays a central regulatory role in the BCR pathway [2]. Ibrutinib, the firstgeneration BTK inhibitor, has shown excellent antitumor activity in both indolent and aggressive B-cell lymphoma. In recent decades, the efficacy and safety of ibrutinib monotherapy or combined with other agents have been
explored in different subtypes of B-cell lymphomas [3, 4]. Even ibrutinib monotherapy has been the first-line treatment for some patients suffering symptomatic chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL) or elder/frail patients with primary central nervous system lymphoma (PCNSL) who can not endure high-dose methotrexate [5, 6]. Ibrutinib monotherapy might be enough for them to have a better life quality with well disease control. Furthermore, many researchers tried to combine BTK inhibitors with other agents to achieve deeper and faster remission. In this review, we will focus on the clinical progression and compare the efficacy of ibrutinib monotherapy or combination strategies for the treatment of B-cell lymphoma based on some ongoing or just-completed clinical trials.
*Correspondence: [email protected] 3 Department of Hematology, Shandong Provin
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