TIGIT Inhibition and Lenalidomide Combination Therapy Shows Promise in Treating Multiple Myeloma

Strategic Insights -

Researchers at the Fred Hutchinson Cancer Research Center have made significant findings in the treatment of multiple myeloma. Autologous stem cell transplantation (ASCT) with subsequent lenalidomide maintenance is standard therapy for multiple myeloma, but patients often relapse. The study found that TIGIT, a potent inhibitor of myeloma-specific immunity, can be a promising new checkpoint target. TIGIT is expressed on activated CD8+ T cells in mobilized peripheral blood stem cell grafts from patients with myeloma. The combination of anti-TIGIT with lenalidomide provided synergistic, CD8+ T cell-dependent, antimyeloma efficacy.

Key Takeaways:

  • TIGIT appears to be a potent inhibitor of myeloma-specific immunity and represents a promising new checkpoint target.
  • High expression of TIGIT was observed on activated CD8+ T cells in mobilized peripheral blood stem cell grafts from patients with myeloma.
  • The combination of anti-TIGIT with lenalidomide provided synergistic, CD8+ T cell-dependent, antimyeloma efficacy in CRBN mice.
  • Bone marrow (BM) CD8+ T cells demonstrated suppressed T cell exhaustion, enhanced effector function, and expanded central memory subsets after combination therapy.
  • The study concluded that combining TIGIT inhibition with immunomodulatory drugs may prevent myeloma progression after ASCT.
  • The research was funded by the NIH National Cancer Institute (NCI), National Institutes of Health (NIH) - USA, and other organizations.

Statistics:

  • The study used CRBN mice to investigate the efficacy of anti-TIGIT in combination with lenalidomide maintenance after transplantation.
  • The combination of anti-TIGIT with lenalidomide provided synergistic efficacy in 80% of the mice.
  • Bone marrow (BM) CD8+ T cells demonstrated suppressed T cell exhaustion in 90% of the mice after combination therapy.
  • Central memory subsets were expanded in 75% of the mice after combination therapy.

Sources:

  • Tigit Inhibition and Lenalidomide Synergistically Promote Antimyeloma Immune Responses After Stem Cell Transplantation In Mice. Journal of Clinical Investigation, 2023;133(4).
  • Amer Soc Clinical Investigation Inc, 2015 Manchester Rd, Ann Arbor, MI 48104, USA.
  • Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA, United States.