RESIDUAL SERUM CONCENTRATIONS OF RITUXIMAB ARE ASSOCIATED WITH RELAPSE RISK IN CHRONIC LYMPHOCYTIC LEUKEMIA
(Abstract release date: 05/18/17)
EHA Library. Tempescul A. 05/18/17; 182481; PB1767
Dr. Adrian Tempescul
Contributions
Contributions
Abstract
Abstract: PB1767
Type: Publication Only
Background
Rituximab is an anti-CD20 chimeric monoclonal antibody approved in first-line treatment of patients with chronic lymphocytic leukemia (CLL), in association with chemotherapy. Rituximab displays a time-dependant pharmacokinetic with a high variability between patients that is primarily related to target mediated elimination.
Aims
Rituximab pharmacokinetics has been associated with clinical response but there is no data on its association with patients’ evolution after immunochemotherapy, which is the aim of the present study.
Methods
Residual serum concentrations of rituximab were determined by an enzyme-linked immunosorbent assay (ELISA) for 35 CLL patients before each infusion, administrated every 28 days at T0, T1, T2, T3, T4, T5. Response and relapse criteria were evaluated according to the International Workshop on Chronic Lymphocytic Leukemia guidelines.
Results
Patients were assigned to two groups related to time to relapse. The first group (n=7), had an early relapse in less than 3 years, the second group (n=28), in more than 3 years. A lower residual serum rituximab concentration was observed in patients with an early relapse and statistical significance was reached for the values obtained after the 3rd cycle (T3) (p=0.02). Concerning the area under the curve (AUC), the difference was significant across all the cycles, an early relapse being associated with a low AUC
(AUCmeanA=1.28 ±1.01 mg/L*day, AUCmeanB=2.79±1.93 mg/L*day, p=0.02). Additionally, the residual rituximab serum concentration between T2 and T5, superior at 70µg/ml, is associated with a long response time, with a sensibility of 100% and a specificity of 52%.
Low residual serum rituximab concentrations in the early relapse group were associated with a higher expression of CD38 and a more frequent administration of the chemotherapy rituximab-bendamustine than rituximab-fludarabine-cyclophosphamide. On the other hand, there was no association with age, sex, cytogenetics, tumour burden or with FCGR3A-158VF polymorphism.
Conclusion
In conclusion, serum residual rituximab concentration in patients with CLL has an impact on clinical evolution after treatment. This study provides data that sustains the need of rituximab serum concentration adaptation in certain CLL patients, in order to reduce relapse risk.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Rituximab, Clinical outcome, Chronic Lymphocytic Leukemia
Abstract: PB1767
Type: Publication Only
Background
Rituximab is an anti-CD20 chimeric monoclonal antibody approved in first-line treatment of patients with chronic lymphocytic leukemia (CLL), in association with chemotherapy. Rituximab displays a time-dependant pharmacokinetic with a high variability between patients that is primarily related to target mediated elimination.
Aims
Rituximab pharmacokinetics has been associated with clinical response but there is no data on its association with patients’ evolution after immunochemotherapy, which is the aim of the present study.
Methods
Residual serum concentrations of rituximab were determined by an enzyme-linked immunosorbent assay (ELISA) for 35 CLL patients before each infusion, administrated every 28 days at T0, T1, T2, T3, T4, T5. Response and relapse criteria were evaluated according to the International Workshop on Chronic Lymphocytic Leukemia guidelines.
Results
Patients were assigned to two groups related to time to relapse. The first group (n=7), had an early relapse in less than 3 years, the second group (n=28), in more than 3 years. A lower residual serum rituximab concentration was observed in patients with an early relapse and statistical significance was reached for the values obtained after the 3rd cycle (T3) (p=0.02). Concerning the area under the curve (AUC), the difference was significant across all the cycles, an early relapse being associated with a low AUC
(AUCmeanA=1.28 ±1.01 mg/L*day, AUCmeanB=2.79±1.93 mg/L*day, p=0.02). Additionally, the residual rituximab serum concentration between T2 and T5, superior at 70µg/ml, is associated with a long response time, with a sensibility of 100% and a specificity of 52%.
Low residual serum rituximab concentrations in the early relapse group were associated with a higher expression of CD38 and a more frequent administration of the chemotherapy rituximab-bendamustine than rituximab-fludarabine-cyclophosphamide. On the other hand, there was no association with age, sex, cytogenetics, tumour burden or with FCGR3A-158VF polymorphism.
Conclusion
In conclusion, serum residual rituximab concentration in patients with CLL has an impact on clinical evolution after treatment. This study provides data that sustains the need of rituximab serum concentration adaptation in certain CLL patients, in order to reduce relapse risk.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Rituximab, Clinical outcome, Chronic Lymphocytic Leukemia
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