Immune biomarkers of increased infection risk in multiple myeloma

Infection remains a leading cause of morbidity in multiple myeloma. Preventing infections is paramount and immune profiling could reflect the cumulative effect of host-, tumor-, and treatment-related immunosuppression. However, current understanding of immune dysfunction and its association with infection is limited. To address this gap in knowledge and identify immune biomarkers of increased infection risk, we performed immune profiling using next-generation flow cytometry in bone marrow and peripheral blood samples from 1786 patients at various disease stages and treatment scenarios. Patients developing infection had significantly lower percentages of CD27+ B cells and CD27- natural killer cells, as well as an increased CD27-/CD27+ T-cell ratio in the bone marrow. These immune risk factors were validated in 3 independent data sets. An immune score was developed to stratify patients with ≤1 vs ≥2 of the aforementioned risk factors, which was associated with higher infection incidence (35% vs 60%, P< .001). The immune score (odds ratio, 2.31; P< .001), disease stage, and CD38-, B-cell maturation antigen-, or G protein-coupled receptor class C group 5 member D-targeted therapy were independently associated with infection incidence. All cell types detectable in the bone marrow and peripheral blood were significantly correlated, suggesting that immune biomarkers of increased infection risk could be monitored using minimally invasive methods that are available in routine laboratories.