Promising therapies for the treatment of chronic lymphocytic leukemia

Abstract

Newer compounds with different mechanisms of action, such as B-cell receptor signal transduction inhibitors, lenalidomide, next generation mAbs and several pro-apoptotic molecules, have shown efficacy in relapsed or refractory CLL patients. Several studies are under way to investigate the efficacy of combinations of these novel drugs. Hopefully, the combined use of these molecules in risk-adapted treatment strategies will change the therapeutic approach in the near future and will pave the way for a long-term control of CLL.

Real‐world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres

“…As this registry enrolled patients between 2010 and 2014, and enrolment in clinical trials was low (<5%), very few patients were treated with investigational kinase inhibitor therapies. The approval of agents, such as ibrutinib and idelalisib, by the United States Food and Drug Administration has transformed the management of CLL, particularly for patients with relapsed/refractory (R/R) disease, unfavourable prognostic factors, or advanced age (for whom CIT regimens may be too toxic) (Grosicki, ; Morabito et al , ,b; Tucker & Rule, ). Landmark studies that contributed to these approvals and their widespread adoption included randomized comparisons against agents such as chlorambucil, ofatumumab, and rituximab (Byrd et al , ; Furman et al , ; Sharman et al , ; Hillmen et al , ).…”

Histone deacetylase inhibitors interrupt HSP90•RASGRP1 and HSP90•CRAF interactions to upregulate BIM and circumvent drug resistance in lymphoma cells

“… 1 – 3 These and additional HDAC inhibitors are currently undergoing clinical testing in various neoplasms, including B-cell lymphomas, where they have shown clinical activity. 3 – 8 As a class, these agents inhibit deacetylation of lysines in multiple proteins, including histones, and enhance transcription of a wide range of genes. 9 – 11 This altered transcription is widely thought to contribute to the antineoplastic effects of HDAC inhibitors, including in B cell neoplasms, 6 , 11 although other mechanisms have also been proposed.…”

Engineering extracellular vesicles as novel treatment options: exploiting herpesviral immunity in CLL

“…Chronic lymphocytic leukaemia (CLL) of B‐cell origin is the most common adult leukaemia in the Western hemisphere. Despite considerable therapeutic improvements throughout the last years [10–12], the disease remains incurable. CLL is characterized by a number of peculiarities: leukaemic B cells express high levels of surface MHC class I and II molecules but lack expression of important accessory and co‐stimulatory molecules [13].…”