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Clinical response and pharmacokinetics of bendamustine as a component of salvage R-B(O)AD therapy for the treatment of primary central nervous system lymphoma (PCNSL)

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Authors
Kim, Therasa; Choi, He Yun; Lee, Hyun-Seo; Jung, Sung-Hoon; Ahn, Jae-Sook; Kim, Hyeoung-Joon; Lee, Je-Jung; Yoo, Hee-Doo; Yang, Deok-Hwan
Issue Date
2018-07-09
Citation
BMC Cancer, 18(1):729
Keywords
BendamustineCSFPharmacokineticsPrimary CNS lymphomaSalvage therapy
Abstract
Background
A relatively high proportion of patients diagnosed with primary CNS lymphoma will experience recurrent disease, yet therapy options are limited in salvage therapy. This is the first study to evaluate a bendamustine-based combination regimen for the treatment of relapsed/refractory PCNSL and to characterize bendamustine pharmacokinetics in the human CSF.

Methods
Patients received bendamustine 75 mg/m2 for two days as part of R-B(O)AD administered intravenously every 4 weeks for up to 4 cycles. Response and adverse events of the regimen were assessed. A sparse sampling strategy and population based modeling approach was utilized for evaluation of plasma and CSF levels of bendamustine.

Results
Ten patients were enrolled into study of whom 70% were of refractory disease and with high IELSG prognostic risk scores. The ORR of R-BOAD was 50% (95% CI, 0.24 to 0.76) with one patient achieving CR and four PR. Primary toxicity of the regimen was reversible myelosuppression, mostly grade 3 or 4 neutropenia. The Cmax mean for plasma and CSF were 2669 ng/mL and 0.397 ng/mL, respectively, and patients with response at deep tumor sites displayed higher trends in peak exposure. Pharmacokinetic data was best described by a four-compartment model with first-order elimination of drug from central plasma and CSF compartments.


Conclusions
R-BOAD is an effective salvage option for PCNSL, but with significant hematologic toxicity. Bendamustine CSF levels are minimal; however correspond to plasma exposure and response.

Trial registration
ClinicalTrials.gov
NCT03392714

; retrospectively registered January 8, 2018.
ISSN
1471-2407
Language
English
URI
http://hdl.handle.net/10371/143517
DOI
https://doi.org/10.1186/s12885-018-4632-y
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College of Pharmacy (약학대학)Research Institute of Pharmaceutical Sciences (종합약학연구소)Journal Papers (저널논문_종합약학연구소)
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