Combining TIGIT inhibition with immunomodulary drugs may prevent MM progression after SCT

Minnie SA, Waltner OG, Ensbey KS, et al. TIGIT Inhibition and Lenalidomide Synergistically Promote Anti-Myeloma Immune Responses After Stem Cell Transplantation in Mice. Journal of Clinical Investigation. 2022; (doi: 10.1172/JCI157907).

To keep multiple myeloma (MM) from progressing despite stem cell transplantation, researchers see promise in coupling routine lenalidomide maintenance with blockade of the inhibitory receptor TIGIT. This immune checkpoint highly expressed on activated CD8 T cells in transplant recipients is believed to deflect myeloma-specific immunity, which is associated with prolonged progression-free survival, and to contribute to immune escape. To gauge the value of TIGIT antibody plus lenalidomide post-transplant, investigators tested MM-bearing mice. They found the dual intervention produced synergistic anti-myeloma immunity by suppressing T cell exhaustion, boosting effector function, and expanding central memory subsets. The level of anti-tumor efficacy associated with TIGIT antibody is tied to Fc-receptor engagement. With favorable data to support the combination of TIGIT inhibition and immunomodulatory drugs (IMiDs), enrollment is underway for a clinical trial that will study outcomes in a sample of patients with relapsed/refractory myeloma treated with an Fc-enabled TIGIT antibody and iberdomide, a next-generation IMiD.

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Tags: myeloma, multiple myeloma, stem cell transplantation, Immunity, transplantation, Survival, Stem Cells, trial, Stem Cell, Research, Transplant, recipients, posttransplant, mice, tumor, transplantation and cellular therapy, antitumor, antibody, stem cell transplant

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