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PHARMACOKINETICS OF RITUXIMAB IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA
Author(s):
Samo Rožman
,
Samo Rožman
Affiliations:
Pharmacy Department,INSTITUTE OF ONCOLOGY LJUBLJANA,Ljubljana,Slovenia;Department of Biopharmaceutics and Pharmacokinetics,Faculty of Pharmacy, University of Ljubljana,Ljubljana,Slovenia
Iztok Grabnar
,
Iztok Grabnar
Affiliations:
Department of Biopharmaceutics and Pharmacokinetics,Faculty of Pharmacy, University of Ljubljana,Ljubljana,Slovenia
Srdjan Novaković
,
Srdjan Novaković
Affiliations:
Department of Molecular Diagnostics,INSTITUTE OF ONCOLOGY LJUBLJANA,Ljubljana,Slovenia
Aleš Mrhar
,
Aleš Mrhar
Affiliations:
Department of Biopharmaceutics and Pharmacokinetics,Faculty of Pharmacy, University of Ljubljana,Ljubljana,Slovenia
Barbara Jezersek Novakovic
Barbara Jezersek Novakovic
Affiliations:
Department of Medical Oncology,INSTITUTE OF ONCOLOGY LJUBLJANA,Ljubljana,Slovenia
(Abstract release date: 05/18/17) EHA Library. Jezersek Novakovic B. 05/18/17; 182420; PB1706
B. Jezersek Novakovic
B. Jezersek Novakovic
Contributions
PDF Abstract
Abstract

Abstract: PB1706

Type: Publication Only

Background

Rituximab dosing is based on evidence from clinical practice rather than from consideration of pharmacokinetics and factors influencing individual exposure. Clinical use of rituximab can be improved through a more individualized treatment.

Aims
The objective of this investigation was to typify rituximab pharmacokinetics in 29 newly diagnosed patients with the diffuse large B-cell lymphoma who received rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every three weeks. The association of rituximab pharmacokinetics with clinical outcome was also investigated.

Methods

Rituximab serum levels were defined by enzyme-linked immunosorbent assay and assessed by a population pharmacokinetic analysis applying the non-linear mixed effects modelling.

Results

A 2-compartment model comprising linear non-specific clearance of 0.252 (95% CI: 0.227 – 0.279) L/day and time-varying specific clearance of 0.278 (95% CI: 0.181 – 0.390) L/day, corresponding to target-mediated drug disposition of rituximab was recognised to best describe the data. The nonspecific clearance was found to be lower in older patients and those with lower body weight. Additionally, the central compartment volume was higher in males. An unambiguous association of clinical response with rituximab pharmacokinetics has been detected. The rate constant of specific clearance decay was 0.143 day-1 (95% CI: 0.0478 – 0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4 – 95.0).

Conclusion
These results imply that time-changes in clearance could serve as a predictive marker of response to rituximab. Our findings prove the rationale for studies evaluating higher doses of rituximab in selected patients.

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Pharmacokinetic, Diffuse large B cell lymphoma, Clinical outcome, Rituximab

Abstract: PB1706

Type: Publication Only

Background

Rituximab dosing is based on evidence from clinical practice rather than from consideration of pharmacokinetics and factors influencing individual exposure. Clinical use of rituximab can be improved through a more individualized treatment.

Aims
The objective of this investigation was to typify rituximab pharmacokinetics in 29 newly diagnosed patients with the diffuse large B-cell lymphoma who received rituximab in combination with cyclophosphamide, doxorubicin, vincristine and methylprednisolone every three weeks. The association of rituximab pharmacokinetics with clinical outcome was also investigated.

Methods

Rituximab serum levels were defined by enzyme-linked immunosorbent assay and assessed by a population pharmacokinetic analysis applying the non-linear mixed effects modelling.

Results

A 2-compartment model comprising linear non-specific clearance of 0.252 (95% CI: 0.227 – 0.279) L/day and time-varying specific clearance of 0.278 (95% CI: 0.181 – 0.390) L/day, corresponding to target-mediated drug disposition of rituximab was recognised to best describe the data. The nonspecific clearance was found to be lower in older patients and those with lower body weight. Additionally, the central compartment volume was higher in males. An unambiguous association of clinical response with rituximab pharmacokinetics has been detected. The rate constant of specific clearance decay was 0.143 day-1 (95% CI: 0.0478 – 0.418) in patients with no disease progression, while in patients with disease progression it was 82.2% lower (95% CI: 33.4 – 95.0).

Conclusion
These results imply that time-changes in clearance could serve as a predictive marker of response to rituximab. Our findings prove the rationale for studies evaluating higher doses of rituximab in selected patients.

Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Pharmacokinetic, Diffuse large B cell lymphoma, Clinical outcome, Rituximab

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