Revisiting checkpoint inhibitors for myeloma: maintenance after stem cell transplant

Multiple myeloma is a hematologic malignancy of plasma cells that manifests with bone marrow tumors causing lytic bone lesions. Autologous stem cell transplantation (ASCT) after high-dose chemotherapy and followed by prolonged maintenance therapy with lenalidomide (LEN) is an effective standard-of-care therapy for multiple myeloma. However, most patients ultimately relapse. Rational combination strategies that address immune dysfunction may prolong the durability of ASCT. In this issue of the JCI, Minnie and colleagues investigated the addition of a checkpoint inhibitor to LEN maintenance therapy after ASCT. They found that the immune checkpoint TIGIT was an optimal target in patient samples. In a syngeneic, immunocompetent multiple myeloma mouse model, blockade of TIGIT synergized with LEN maintenance by inducing immune protection, characterized in part by the expansion of polyfunctional T cells in the bone marrow. The treatment enhanced durable antimyeloma efficacy and has translatable implications.

Automated summary

Multiple myeloma is a malignant disease characterized by bone marrow tumors and bone lesions. Autologous stem cell transplantation followed by lenalidomide maintenance therapy is the standard treatment for multiple myeloma. However, relapse is common. In this study, the addition of a checkpoint inhibitor to lenalidomide maintenance therapy was investigated and found to enhance the immune response and improve the efficacy of the treatment in a mouse model of multiple myeloma.