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Serum BLyS levels increase after rituximab as initial therapy in patients with follicular Grade 1 non-Hodgkin lymphoma.

ABSTRACT: Serum B-lymphocyte stimulator (BLyS) levels are elevated in a subset of non-Hodgkin lymphoma (NHL) patients, particularly those with a family history of B-cell malignancies or a polymorphism in the BLyS gene. BLyS promotes growth of malignant B-cells and increased serum BLyS levels are associated with a poor clinical outcome. In this study, BLyS levels were measured before and after 4 weekly doses of rituximab in 30 patients with previously untreated follicular Grade 1 NHL. A significant increase was seen in the serum levels of BLyS (P = 0.0001) after rituximab therapy. The increase was independent of genetic variability in the BLyS gene.

SUBMITTER: Ansell SM

PROVIDER: S-EPMC2774736 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Serum BLyS levels increase after rituximab as initial therapy in patients with follicular Grade 1 non-Hodgkin lymphoma.

Ansell Stephen M SM Novak Anne J AJ Ziesmer Steven S Price-Troska Tammy T LaPlant Betsy B Dillon Stacey R SR Witzig Thomas E TE

American journal of hematology 20090201 2

Serum B-lymphocyte stimulator (BLyS) levels are elevated in a subset of non-Hodgkin lymphoma (NHL) patients, particularly those with a family history of B-cell malignancies or a polymorphism in the BLyS gene. BLyS promotes growth of malignant B-cells and increased serum BLyS levels are associated with a poor clinical outcome. In this study, BLyS levels were measured before and after 4 weekly doses of rituximab in 30 patients with previously untreated follicular Grade 1 NHL. A significant increas ...[more]

PMID: 19051265

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Project description:Treatment of follicular lymphoma with rituximab is currently recommended at a dose of 375 mg/m(2). We aimed to provide a rationale for optimal dosing and scheduling of this anti-CD20 antibody based on pharmacokinetics.Clinical efficacy of immunochemotherapy with rituximab, fludarabine and mitoxantrone followed by 2-monthly rituximab maintenance was evaluated in 29 patients with previously untreated follicular lymphoma in a prospective phase II trial (AGMT-NHL9). Pharmacokinetic analysis was assessed in 17 patients.Induction treatment resulted in high clinical response rates (complete remission 66%; ORR 100%). Significantly higher complete remission rates were observed in female patients (86 vs. 47%; Odds Ratio 6.8, 95% CI: 1.12; 41.82; P=0.05). Rituximab pharmacokinetic analysis showed a high variability ranging over almost 1 order of magnitude at maintenance cycle 1 (area under the curve 1,540-12,025 g/L*days). Median area under the curve was lower in men (81%) and in patients with initial bone marrow infiltration (76%). Higher rituximab serum concentrations before next therapy (C(trough)) were associated with female sex (P=0.04) as well as with absence of initial bone marrow infiltration (P=0.001). C(trough) correlated with remission quality (complete vs. partial remission; P=0.005) and progression-free survival (P=0.03). A decline in rituximab C(trough) below 25,000 ng/mL was observed 9.5 to 62 months before clinical relapse (P=0.008).The results of this pilot trial suggest that more differentiated dosing schedules based on gender and bone marrow infiltration should be explored for rituximab therapy for lymphoma. This study was registered in ClinicalTrials.gov (Identifier: NCT01560117).

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Prediagnostic serum levels of cytokines and other immune markers and risk of non-hodgkin lymphoma.

Project description:Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, and TNF-?] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein, and sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. ORs and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated by using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR = 1.7, 95% CI: 1.1-2.8; P(trend) = 0.02) and sCD27 (OR = 5.3, 95% CI: 2.9-9.4; P(trend) < 0.0001). These associations remained in analyses of cases diagnosed longer than 6 years following blood collection (sTNF-R1: OR = 2.1, 95% CI: 1.0-4.0, P(trend) = 0.01; sCD27: OR = 4.1, 95% CI: 1.9-8.5, P(trend) = 0.0001). Elevated levels of IL-10, TNF-? and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis and were null for cases diagnosed longer than 6 years postcollection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states, respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis.

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