Immunotherapy for chronic lymphocytic leukemia in the era of BTK inhibitors

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.