Immunomodulatory Effects in a Phase II Study of Lenalidomide Combined with Cetuximab in Refractory <i>KRAS</i>-Mutant Metastatic Colorectal Cancer Patients

<div><p></p><p>This study assessed the immunomodulatory effects in previously treated <i>KRAS</i>-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.</p><p>Trial Registration</p><p><a href="http://clinicaltrials.gov/show/NCT01032291" target="_blank">ClinicalTrials.gov NCT01032291</a></p></div

Significantly regulated cell populations in the lenalidomide plus cetuximab arm.

*<p>Cell populations that are unique to the lenalidomide plus cetuximab arm only.</p><p>Abs, absolute; C1D1, cycle 1 day 1; C2D1, cycle 2 day 1; C3D1, cycle 3 day 1; FC, fold change; NK, natural killer.</p

Study design and enrollment in patient groups.

<p>Study was terminated before the expansion part of phase IIb. *One patient was randomized to the lenalidomide monotherapy group but discontinued before taking any study drug and was therefore excluded from the analyses. AE, adverse event; ITT, intention to treat; PD, progressive disease.</p

Significantly regulated cell populations in the lenalidomide monotherapy arm.

*<p>Cell populations that are unique to the lenalidomide monotherapy arm only.</p><p>Abs, absolute; C1D1, cycle 1 day 1; C2D1, cycle 2 day 1; C3D1, cycle 3 day 1; FC, fold change; NK, natural killer.</p

Patient baseline characteristics.

<p>ECOG PS, Eastern Cooperative Oncology Group performance status.</p

Significantly regulated cell populations in all subjects.

<p>Abs, absolute; C1D1, cycle 1 day 1; C2D1, cycle 2 day 1; C3D1, cycle 3 day 1; FC, fold change; NK, natural killer.</p