B-cell receptor pathway modulators in NHL

Abstract

With the recent success of the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, and the phosphoinositide-3-kinase (PI3K) inhibitor, idelalisib, in the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a number of new agents targeting the B-cell receptor (BCR) pathway are in clinical development. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. This review will summarize the current data with the use of single agent and combination therapy with BCR inhibitors in NHL. In addition, commonly encountered as well as serious toxicities and hypothesized resistance mechanisms will be discussed. Lastly, this review will examine the future of these agents and opportunities to maneuver them into the front-line setting in selected NHL subtypes.

Non-Hodgkin lymphoma

“…Early phase I and II clinical trials have shown beneficial effects, such as for ibrutinib in treating mantle cell lymphoma 34. However, acquired resistance and unexpected toxicities are common, and there is still much to learn in terms of how these drugs should be used.…”

An Empirical Study of the Prescription Pattern of Drugs for Hematological Malignancies in Japan from 2010–2014

“…4). Indeed, recent advances in the understanding of disease biology, for instance, B-cell receptor modulators, including ibrutinib, an inhibitor of Bruton's tyrosine kinase, and idelalisib, an inhibitor of phosphatidylinositol 3-kinase for NHL, 28) and immune approaches, including checkpoint blockade with anti-PD-1 antibodies and adoptive cellular therapy with chimeric antigen receptor T cells for ALL and myeloma, 29) have been seen on the global level. This study confirm the same trends in Japan, and the availability of these new drugs and biological products is expected to improve in the near future, thereby providing new treatment options for existing patients, as well as advances in health care for the entire Japanese population.…”

Interrogating B cell signaling pathways: A quest for novel therapies for mantle cell lymphoma

“…Through CD19 and adaptor protein-mediated recruitment of PI3K, BCR signals ultimately lead to the activation of the prosurvival signaling effectors AKT and NF-В ( Fig. 2) (51). Various PI3K-AKT inhibitors are active in preclinical studies and preliminary trials, with idelalisib emerging as one of the frontrunners (Fig.…”