Ibrutinib in B-cell lymphoma: single fighter might be enough?

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 well-tolerated 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 receptor (BCR) signaling pathway; B-cell lymphoma; Bruton’s tyrosine kinase (BTK); Ibrutinib; Monotherapy.

Fig. 1

Structure of Bruton’s tyrosine kinase (BTK) and associated cross-linking signaling pathways. a BTK comprises five structural domains. BTK activation occurs twice during phosphorylation upon the plasma membrane. The first phosphorylation occurs on the Tyr551 site within the kinase domain by the Syk or Src family kinase, which subsequently leads to autophosphorylation of Tyr223 in the SH3 domain, achieving full activation of BTK kinase activity. b BTK activation process and inhibited result of cross-linking pathways by BTK inhibitors. The left figure shows when extracellular antigen bond BCR, BTK can regulate adverse cellular biological processes by activating multiple important pathways, such as NF-kB, MAPK, NFAT, and mTOR pathway. The right figure shows when the BCR pathway is irreversibly inhibited by small-molecule BTK inhibitors, its downstream pathway such as NF-kB, MAPK, and NFAT will also be inhibited, resulting in anti-tumor activity in B cell lymphoma