Preclinical and clinical efficacy of the HDAC6 inhibitor ricolinostat in combination with BCR pathway inhibitors in relapsed/refractory chronic lymphocytic leukemia

Despite the impact of targeted therapies such as BTK and BCL2 inhibitors in chronic lymphocytic leukemia (CLL), drug resistance and relapse remain major challenges, underscoring the need for alternative therapies with unique mechanisms of action [ 1 , 2 , 3 , 4 , 5 ]. Ricolinostat is a potent HDAC6 inhibitor that increases α-tubulin and histone H3 acetylation, the latter via class I HDAC inhibition [ 6 , 7 ]. In vitro and in vivo studies have demonstrated that HDAC inhibitors induce apoptosis in CLL cells and reduce tumor burden [ 8 , 9 ]. In this study, we report the preclinical and clinical efficacy of ricolinostat in combination with B-cell receptor (BCR) pathway inhibitors ibrutinib and idelalisib in relapsed/refractory (R/R) CLL.