Laboratory Correlates and a Phase I Clinical Trial of Lenalidomide in Combination with Plerixafor in Patients with Previously Treated Chronic Lymphocytic Leukemia

The microenvironment emerged as an attractive therapeutic target for chronic lymphocytic leukemia (CLL) given increasing evidence of its essential role in CLL cell survival. Plerixafor, a small molecule inhibitor of the CXCR4 receptor, is responsible for homing CLL to the microenvironment via a concentration gradient of its cognate ligand CXCL12 and has been safely tested in CLL patients. Lenalidomide is an immunomodulatory small molecule with efficacy in CLL, though monotherapy responses are typically partial and delayed. The combination of plerixafor with lenalidomide offers a novel non-cytotoxic alternative to improve clinical activity. Laboratory correlatives were designed to improve understanding of the effects of individual and combination therapy on the biology of CLL, assess for CLL mobilization from the microenvironment, and discover targetable drug resistance mechanisms to improve therapeutic efficacy.