Significant Increase in Peripheral NK Cells May Support Lenvatinib Efficacy in Advanced Thyroid Cancer


A prospective study of blood samples confirmed the immune-modulatory effect of lenvatinib with a significant increase in the peripheral natural killer cells among patients with advanced thyroid cancer.

A prospective collection of blood from patients with RAI-refractory, advanced thyroid cancer treated with lenvatinib (Lenvima) showed a significant increase in the peripheral natural killer (NK) cell population, confirming the immune-modulatory activities of the agent, according to a poster presentation at the 91st Annual Meeting of the American Thyroid Association.1

“This finding confirms the immune-modulatory effect of lenvatinib, which might be associated with lenvatinib efficacy,” Min Ji Jeon, MD, PhD, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, said in a presentation of the data.

From February 2020 to July 2021, investigators prospectively collected blood samples (20 ccs of whole blood) at 2- to 3-month intervals, 2 to 4 times from each patient. Of the 10 patients included, 4 were enrolled before treatment and 6 were enrolled while receiving lenvatinib.

In total, 31 blood samples were obtained, including 4 pre-treatment samples, 23 on-treatment samples, and 4 off-treatment samples. “There are 4 off-treatment samples obtained during the drug interruption period due to the side effects of lenvatinib,” investigators wrote in the abstract.

Investigators then separated peripheral blood mononuclear cells (PBMC), and they conducted mass cytometry analyses. PBMC profiles were compared, including CD8-positive cells, CD4-positive cells, B cells, NK cells, monocytes, dendritic cells, and lymphocyte to monocyte ratios.

At baseline, patients were a median age of 64.5 years (range, 60.3-68.5). The majority of patients were female (60%), had papillary thyroid carcinoma (60%), and stage IV disease (67%). The cumulative RAI dose was 240 mCi (range, 163-519). Two patients (20%) were previously treated with sorafenib (Nexavar). Lymph nodes were the target lesion in 50% of patients.

The median dose of lenvatinib maintenance among those treated was 19 mg (range, 14-20). Median duration between the initiation of lenvatinib treatment to the first blood sampling was 27 months.

Best response from lenvatinib was stable disease in 8 patients (80%) and partial response in 2 patients (20%).

When comparing PBMC profiles of pre-treatment, on-treatment, and off-treatment samples, only peripheral NK cell proportion differed significantly in the cell proportion of total live cells (9.3 [4.5%] vs 20.8 [7.9%] vs 13.3 [3.1%], respectively. The P values of pre-treatment vs on-treatment and pre-treatment vs off-treatment were .009 and .07, respectively. These data were further confirmed when evaluating early and late NK cells. “The levels of cytokines associated with the NK cell proliferation, IL-2, IL-10, IL-15, and TGF-beta were analyzed, but there were no significant changes in all these cytokines,” investigators wrote in the abstract.

“Further large studies are needed to confirm our findings and elucidate the mechanism,” Jeon concluded.

Jin M, Kim CA, Jun BD, et al. Changes in Peripheral Blood Immune Cell Population in Thyroid Cancer Patients treated with Lenvatinib. Thyroid. 2022;32(1):P-1-A-135. doi:10.1089/thy.2022.29137.abstracts.
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