Lessons learned from checkpoint blockade targeting PD-1 in multiple myeloma
Immune checkpoints and agonists modulate ongoing, antigen-specific immune responses.
Therapeutic blockade of CTLA-4, PD-1, and PD-L1 has proven to be an effective treatment
approach for a subset of patients with a variety of cancers of epithelial, mesenchymal, or
hematologic origin. In multiple myeloma, a B-cell lymphoid malignancy of terminally
differentiated plasma cells, PD-1 pathway blockade is ineffective as a single agent. The
initial promise in combination approaches utilizing anti–PD-1 with the immunomodulatory …
Therapeutic blockade of CTLA-4, PD-1, and PD-L1 has proven to be an effective treatment
approach for a subset of patients with a variety of cancers of epithelial, mesenchymal, or
hematologic origin. In multiple myeloma, a B-cell lymphoid malignancy of terminally
differentiated plasma cells, PD-1 pathway blockade is ineffective as a single agent. The
initial promise in combination approaches utilizing anti–PD-1 with the immunomodulatory …
Abstract
Immune checkpoints and agonists modulate ongoing, antigen-specific immune responses. Therapeutic blockade of CTLA-4, PD-1, and PD-L1 has proven to be an effective treatment approach for a subset of patients with a variety of cancers of epithelial, mesenchymal, or hematologic origin. In multiple myeloma, a B-cell lymphoid malignancy of terminally differentiated plasma cells, PD-1 pathway blockade is ineffective as a single agent. The initial promise in combination approaches utilizing anti–PD-1 with the immunomodulatory drugs, lenalidomide or pomalidomide, was not confirmed in randomized trials. Here, we explore available data for and against manipulation of the PD-1 pathway and other immune checkpoints in myeloma and highlight several promising concepts and challenges that face ongoing development of immunotherapeutics for this disease.
AACR