In early clinical trials, small-molecule inhibitors of the B-cell signal transduction have demonstrated improvement in response rates in elderly patients with CLL, suggesting that they may become an effective treatment option for this subset of patients. These agents, when available, will eventually allow clinicians to move from chemotherapy to targeted therapy therefore avoiding several toxicities associated with chemotherapy.
Ibrutinib (PCI-32765) is the most developed among these emerging agents. In addition to the benefits observed in the elderly population, ibrutinib seems to be active also in a subset of patients with a chromosome 17p deletion, considered a high-risk population of patients with a poor outcome.[54–56] GS-1101, formerly known as CAL-101, has been explored as a monotherapy and in combination with other agents.[57,106] Finally, ABT-199, a bcl-2 inhibitor has also shown activity in patients with the 17p deletion.
Also the second-generation monoclonal antibodies promise to modify the paradigm of treatment even in old or unfit patients. Results of this review outline how it is relevant to get more mature results from ongoing clinical trials.
Expert Rev Hematol. 2013;6(4):441-449. © 2013 Expert Reviews Ltd.