ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) is common in patients with multiple myeloma (MM) and is associated with a poor prognosis. We assessed CKD-associated clinical outcomes among elderly patients with MM initiating chemotherapy in the United States. MATERIALS AND METHODS: We identified elderly Medicare beneficiaries (≥66 years) diagnosed with MM who initiated first-line therapy from 2008 to 2014. We identified CKD using diagnosis codes. We followed patients for death, time to next treatment (TTNT), and myeloma-defining events (anemia, hypercalcemia, skeletal-related events, progression to/of CKD) until September 30, 2015. We estimated overall survival, TTNT, and cumulative incidence of myeloma-defining events using the Kaplan-Meier method and risk of CKD-associated outcomes using Cox proportional hazards models, adjusting for demographics and comorbid conditions. RESULTS: Of 22,484 included patients, 8704 (39%) had CKD at first-line therapy initiation. Compared with patients without CKD, patients with CKD had shorter median overall survival (2.1 vs. 3.6 years) and median TTNT (10.0 vs. 12.4, 9.7 vs. 11.2, 8.3 vs. 9.2, and 6.9 vs. 8.3 months at first- to fourth-line therapy). Probability of CKD progression for patients at stages 1 to 5 was higher than the probability of developing CKD for patients without CKD (3-year cumulative incidence [95% confidence interval, CI], 47% [45-48%] vs. 27% [24-26%]). Adjusted hazard ratios for CKD versus non-CKD were: all-cause death, 1.23 (95% CI, 1.18-1.28); anemia, 1.34 (95% CI, 1.24-1.45); hypercalcemia, 1.23 (95% CI, 1.09-1.38); skeletal-related events, 0.85 (95% CI, 0.90-0.91); and TTNT, from 1.03 (95% CI, 0.96-1.10) at third-line therapy to 1.15 (95% CI, 1.04-1.27) at fourth-line therapy. CONCLUSION: Data from the study suggest that CKD-associated clinical burden is substantial in elderly patients with MM.
Subject(s)
Geriatric Assessment , Medicare , Multiple Myeloma/complications , Multiple Myeloma/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Aged , Aged, 80 and over , Cause of Death , Disease Management , Geriatric Assessment/statistics & numerical data , Humans , Incidence , Mortality , Multiple Myeloma/therapy , Patient Outcome Assessment , Prognosis , Proportional Hazards Models , Public Health Surveillance , Retrospective Studies , United States/epidemiologyABSTRACT
AIDS-related Kaposi's sarcoma (AIDS-KS) risk remains substantially elevated compared with the general population, even among patients who receive effective combination antiretroviral therapy. This study investigated the role of inflammatory and immune activating biomarkers in AIDS-KS in men who have sex with men in the Multicenter AIDS Cohort study between 1984 and 2010. Concentrations of 24 serum biomarkers; IL-1ß, IL-2, IL-6, IL-8, IL-10, IL-12p70, sGP130, sIL-2Rα, sIL-6R, eotaxin, MCP-1, MCP4, MIP 1ß, TARC, BLC-BCA1, IP-10, GM-CSF, IFN-γ, BAFF, sCD14, CD27, sTNFR-2, sCRP, and TNF-α were tested longitudinally in 1,501 men. The concentrations of each biomarker were compared between AIDS-KS cases and controls at multiple time points, 0-1 years, 1-2 years, 2-3 year, 3-5 years and over 5 years, prior to KS diagnosis or study termination, using univariate non-parametric Kruskal-Wallis tests and logistic regression, adjusted for HBV and HCV co-infection, race/ethnicity, age at last visit, education, smoking and CD4+ cell count. In univariate analyses, concentrations of four markers were consistently higher in cases; sIL-2Rα, IP-10, sTNFR-2, MCP-1, and five were higher in controls; GM-CSF, IL-6, MIP-1ß, sCRP, sGP130. In the adjusted models concentrations of four markers were significantly inversely associated with AIDS-KS risk including sGP130 (OR=0.14, 95% CI = 0.03-0.73, BAFF (OR=0.60, 95% CI =0.16-0.90), sCRP (OR=0.61, 95% CI = 0.43-0.87) and IL-6 (OR=0.51, 95% CI = 0.35-0.76). These results support a role for markers of immune activation and inflammation in AIDS-KS and may highlight pathways to be targeted for risk stratification or therapeutics.
ABSTRACT
BACKGROUND: Chronic inflammation and immune activation are reported to play a key role in the etiology of non-Hodgkin lymphoma (NHL). We conducted a meta-analysis on the associations between prediagnosis circulating levels of immune stimulatory markers, interleukin 6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), CXCL13, soluble CD23 (sCD23), sCD27, sCD30, and the risk of NHL. METHODS: Relevant studies were identified from PubMed, EMBASE, and Web of Science up to January 1, 2017. We calculated summary odds ratio (OR) estimates for the association between one natural log increase in concentration of each biomarker and NHL using random-effects models for NHL as a composite outcome and for several histological subtypes of NHL. RESULTS: Seventeen nested case control studies were included. Elevated levels of several biomarkers were more strongly associated with increased odds of NHL: TNF-α, OR = 1.18 (95% confidence interval [CI] = 1.04 to 1.34); CXCL13, OR = 1.47 (95% CI = 1.03 to 2.08); sCD23, OR = 1.57 (95% CI = 1.21 to 2.05); sCD27, OR = 2.18 (95% CI = 1.20 to 3.98); sCD30, OR = 1.65 (95% CI = 1.22 to 2.22). In stratified analyses, IL-6, TNF-α, sCD27, and sCD30 were more strongly associated with NHL in HIV-infected individuals compared to HIV-uninfected individuals. Between-study heterogeneity was observed across multiple biomarkers for overall NHL and by subtypes. CONCLUSION: This meta-analysis provides evidence that elevated circulating levels of TNF-α, CXCL13, sCD23, sCD27, and sCD30 are consistently associated with an increased risk of NHL, suggesting the potential utility of these biomarkers in population risk stratification and prediction.
