Levels of CEACAM6 in Peripheral Blood Are Elevated in Patients with Plasma Cell Disorders: A Potential New Diagnostic Marker and a New Therapeutic Target?

INTRODUCTION: The prognosis of multiple myeloma is still unfavorable due to inherent characteristics of the disease and the often-delayed diagnosis due to widespread and unspecific symptoms such as back pain and fatigue. Therefore, a simple diagnostic blood test would be helpful to speed up the diagnostic procedure in such patients (pts.). Here, we evaluated the diagnostic value of plasma levels of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in the peripheral blood and bone marrow of pts. with plasma cell disorders and in healthy controls. MATERIALS AND METHODS: Immunoreactive CEACAM6 was determined in the peripheral blood and bone marrow (n = 95/100) of pts. with monoclonal gammopathy of unknown significance (MGUS: 28/37), newly diagnosed multiple myeloma (NDMM: 42/40), and relapsed/refractory multiple myeloma (RRMM: 25/23) by sandwich ELISA. RESULTS: Median CEACAM6 levels in the peripheral blood of pts. with plasma cell disorders were significantly higher than those of healthy controls (healthy controls: 15.2 pg/ml (12.1-17.1); MGUS: 19.0 pg/ml (16.4-22.5); NDMM: 18.0 pg/ml (13.4-21.2); and RRMM: 18.9 pg/ml (15.2-21.5); p < 0.001). Plasma levels of CEACAM6 discriminated healthy subjects from MGUS/NDMM pts. (AUC = 0.71, 95% CI: 0.6-0.8); i.e., a CEACAM6 level > 17.3 pg/ml has an 82% (95% CI: 70-90) predictive probability for the identification of MGUS or NDMM. Moreover, CEACAM6 levels in the bone marrow were significantly higher in RRMM pts. than in NDMM pts. (p = 0.04), suggesting a role of this molecule in disease progression. CONCLUSION: CEACAM6 plasma levels can noninvasively identify pts. with a plasma cell disorder and should be evaluated prospectively as a potential diagnostic marker. Moreover, due to high CEACAM6 levels in the bone marrow in RRMM pts., this adhesion molecule might be a therapeutic target in multiple myeloma pts.

Fatigue at baseline is associated with geriatric impairments and represents an adverse prognostic factor in older patients with a hematological malignancy.

Prospective data on fatigue in elderly persons with a hematological malignancy are rare. We aimed to determine the prevalence of fatigue and its association with clinical outcome and geriatric impairments in older individuals newly diagnosed with blood cancer. The EORTC QLQ-C30 and a multidimensional geriatric assessment (MGA) were performed in parallel in 149 consecutive patients aged > 67 years (median 77.8 years) at Innsbruck Medical University between January 2009 and April 2016. Fatigue as defined by EORTC QLQ-C30 was the most prevalent symptom (84%) and was significantly associated with self-reported role and physical functioning, global health status and insomnia, dyspnea, and loss of appetite (p < 0.001). Remarkably, pronounced fatigue was associated with impaired performance status and objective functional capacities in MGA, with altered depression scoring, G8 screening, and elevation of serum inflammation markers (p < 0.001). Patients with minor fatigue had a median overall survival (OS) of 26.4 months, whereas those with marked fatigue displayed an OS of 7.0 months (p < 0.001). The association between fatigue and shortened OS was supported in multivariate analyses (HR 1.74, CI 1.09-2.76; p = 0.021). Fatigue is seen to have a high prevalence and to be an adverse prognostic factor in elderly patients with a hematological malignancy. The strong impact of fatigue on clinical performance and OS emphasizes the relevance of patient-reported outcomes in individualized treatment algorithms. Patients will benefit from identification of fatigue, allowing timely interventions. The correlation between fatigue, impaired performance, nutritional status, and inflammation might suggest an underlying common pathway.