Immunomodulatory effects in a phase II study of lenalidomide combined with cetuximab in refractory KRAS-mutant metastatic colorectal cancer patients.
This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA(+) naïve T cells 3-fold while increasing the percentage HLA-DR(+) activated T helper cells and percentage total CD45RO(+) CD8(+) memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001). In addition, lenalidomide decreased the percentage of circulating CD19(+) B cells 2.6-fold (p<0.0001). Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.


BACKGROUND
ClinicalTrials.gov NCT01032291.
Department of Translational Development, Celgene Corporation, Summit, New Jersey, United States of America.
Anita K
AK
Gandhi
Tao
T
Shi
Mingyu
M
Li
Ulf
U
Jungnelius
Alfredo
A
Romano
Josep
J
Tabernero
Salvatore
S
Siena
Peter H
PH
Schafer
Rajesh
R
Chopra
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D000077269:Lenalidomide; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D018631:ras Proteins / Q000235:genetics*
D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D013792:Thalidomide; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000077269:Lenalidomide; D000068818:Cetuximab