br Discussion In this pilot
Discussion In this pilot study, we report that sequential treatment of low dose clofarabine and lenalidomide is safe and feasible for elderly patients with high risk MDS and AML. Only one subject developed dose limiting toxicity (liver dysfunction) from lenalidomide consolidation therapy. Pre-treatment samples uniformly demonstrated high expression of the exhaustion markers (PD1, LAG3, and TIM3) in T muscarinic receptor antagonists which are known to cause functional impairment of T cells. A recent study showed that cancer specific T cells were highly enriched in the PD1+ T cell population . We also found that NK cells had higher expression of LIR1, an inhibitory molecule known to induce impairment of leukemia killing . These findings suggest that both T cells and NK cells are functionally impaired in high risk MDS or AML, possibly due to immune editing by the malignant cells [9,10]. In responders and stable disease subjects clofarabine induced significant lympho-depletion and decreased the numbers of exhausted CD4 T cells and terminally differentiated NK cells with inhibitory markers. However, the dynamics of T cell exhaustion markers were variable during lenalidomide therapy and further study will be needed to elucidate the role of T cell subset profiles in high risk MDS and AML. Small sample size limits the generalization of our findings to clinical practice. Nonetheless our study sheds light on the immune-modulating effects of clofarabine and lenalidomide and suggests that immune profiling can be used to guide treatments aimed at boosting immunity to leukemia in high risk MDS and AML.
Conflict of interest
Acknowledgements We thank all patients who donated the samples to feces study. This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute at the National Institutes of Health (Z01-HL002342-14). Lenalidomide was obtained through Material Cooperative Research and Development Agreement (MCRADA) between Celgene Corporation (New Jersey, USA) and National, Heart, Lung, and Blood Institute, National Institutes of Health.