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)

• Published in: BMC cancer Vol. 18; no. 1; p. 729
• Main 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.07.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Analysis; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bendamustine; Bendamustine Hydrochloride - administration & dosage; Bendamustine Hydrochloride - pharmacokinetics; Cancer therapies; Central nervous system; Central Nervous System Neoplasms - drug therapy; Chemotherapy; CSF; Diagnosis; Dosage and administration; Drug dosages; Drug therapy; Female; Homeopathy; Humans; Lymphoma; Lymphoma - drug therapy; Male; Materia medica and therapeutics; Metabolites; Middle Aged; Nervous system; Neurotoxicity; NMR; Non-Hodgkin's lymphomas; Nuclear magnetic resonance; Pharmacokinetics; Pilot Projects; Plasma; Primary CNS lymphoma; Salvage Therapy; Studies; Therapeutics; Primary CNS lymphoma; Bendamustine; Pharmacokinetics; Salvage therapy; CSF
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4632-y

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. Patients received bendamustine 75 mg/m 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. 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 C 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. 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. ClinicalTrials.gov NCT03392714 ; retrospectively registered January 8, 2018.