Dr McCarthy on Neutrophil-Mediated Immunosuppression in Multiple Myeloma

Philip McCarthy, MD, director, the Blood and Marrow Transplant Program, Roswell Park Comprehensive Cancer Center, discusses findings from an investigation into neutrophils in the tumor microenvironment (TME) of multiple myeloma and their impact on progression-free survival (PFS).

The study evaluated the role of neutrophils in multiple myeloma, which McCarthy notes presents in 3 distinct ways: diffuse bone marrow infiltration, osteolytic lesions, and plasmacytomas, the latter of which are often extramedullary. The goal of the study was to determine if the TME of each area was different, McCarthy says, explaining that osteolytic lesions and plasmacytomas were grouped together and referred to as focal lesions.

At the 2024 EHA Congress, McCarthy and colleagues presented data from this analysis, which included comparisons between healthy donor bone marrow, as well as marrow and focal lesions from patients with multiple myeloma. Using a novel biopsy system developed by Hemn Mohammadpour, DVM, PhD, and Jens Hillengass, MD, PhD, both of Roswell Park Comprehensive Cancer Center, investigators identified significant differences in neutrophil populations between the bone marrow and focal lesions.

Key findings revealed that neutrophils, natural killer (NK) cells, and T cells in focal lesions exhibited distinct phenotypes. McCarthy notes that the evaluation of NK and T cells is ongoing. Regarding the current analysis, abhorrent neutrophils were found in the TME of focal lesions that were not present in the bone marrow of patients with multiple myeloma or in that of healthy donors. Two populations of neutrophils that were unique to focal lesions were associated with inflammatory and immunosuppressive cytokines, contributing to the overall immunosuppressive environment in multiple myeloma due to the suppression of T-cell activation.

McCarthy and colleagues concluded that these unique neutrophils in the TME of focal lesions could affect PFS. Additionally, analyzing these neutrophils could lead to the identification of novel targets and agents for multiple myeloma to improve responses to immune therapy.