Understanding the pathogenesis of CLL has uncovered a plethora of novel targets 
for human application of monoclonal antibodies, engineered T cells, or 
inhibitors of signal transduction pathways. The B-cell receptor signaling 
pathway is being actively explored as a therapeutic target in CLL. Ibrutinib, an 
inhibitor of Bruton's tyrosine kinase is showing impressive responses in heavily 
pre-treated high-risk CLL, whether alone or in combination with MoAbs or 
chemotherapy. Other key components of the BCR pathway, namely PI3K-δ, are also 
being targeted with novel therapies with promising results as well. Future 
trials would likely evaluate ibrutinib in the front-line setting. Moreover, 
improvements in allogeneic HCT mostly by continuing to reduce associated 
toxicity as well as incorporating cellular therapies such as autologous CLL 
tumor vaccines, among others, will continue to expand. This is also the case for 
the next generation of chimeric antigen receptor therapy for CLL once 
genetically modified T cells are available at broad scale and with improved 
efficacy. As our ability to further refine and integrate these therapies 
continues to improve, and we gain further knowledge from gene sequencing, we 
anticipate that treatment algorithms will continue to be revised to a more 
personalized approach to treat this disease with improved efficacy and devoid of 
unnecessary toxicity.