Showing papers by "Anton Hagenbeek published in 2014"
Netherlands Cancer Institute1, University of Würzburg2, Harvard University3, Queen Mary University of London4, University of Barcelona5, Paris 12 Val de Marne University6, Paris Descartes University7, Bosch8, Radboud University Nijmegen9, Claude Bernard University Lyon 110, University of British Columbia11, Karolinska Institutet12
TL;DR: In this paper, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated.
Abstract: The cellular microenvironment in follicular lymphoma is of biological and clinical importance. Studies on the clinical significance of non-malignant cell populations have generated conflicting results, which may partly be influenced by poor reproducibility in immunohistochemical marker quantification. In this study, the reproducibility of manual scoring and automated microscopy based on a tissue microarray of 25 follicular lymphomas as compared to flow cytometry is evaluated. The agreement between manual scoring and flow cytometry was moderate for CD3, low for CD4, and moderate to high for CD8, with some laboratories scoring closer to the flow cytometry results. Agreement in manual quantification across the 7 laboratories was low to moderate for CD3, CD4, CD8 and FOXP3 frequencies, moderate for CD21, low for MIB1 and CD68, and high for CD10. Manual scoring of the architectural distribution resulted in moderate agreement for CD3, CD4 and CD8, and low agreement for FOXP3 and CD68. Comparing manual scoring to automated microscopy demonstrated that manual scoring increased the variability in the low and high frequency interval with some laboratories showing a better agreement with automated scores. Manual scoring reliably identified rare architectural patterns of T-cell infiltrates. Automated microscopy analyses for T-cell markers by two different instruments were highly reproducible and provided acceptable agreement with flow cytometry. These validation results provide explanations for the heterogeneous findings on the prognostic value of the microenvironment in follicular lymphoma. We recommend a more objective measurement, such as computer-assisted scoring, in future studies of the prognostic impact of microenvironment in follicular lymphoma patients.
53 citations
Sarah Cannon Research Institute1, Stanford University2, New York University3, University of Washington4, Oregon Health & Science University5, Georgetown University6, McGill University7, Ludwig Maximilian University of Munich8, University of Amsterdam9, University of Bologna10, Genentech11, Willamette University12
TL;DR: In this paper, an ongoing study of polatuzumab vedotin (PoV) and pinatuzumaab vanet al. (PiV) showed clinical activity in combination with rituximab (R) in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma(FL).
38 citations
University Medical Center Groningen1, University of Nottingham2, Memorial Sloan Kettering Cancer Center3, University of Manchester4, Samsung Medical Center5, Fudan University6, University of Southampton7, GlaxoSmithKline8, Research Triangle Park9, Erasmus University Rotterdam10, Genmab11, University of Amsterdam12
TL;DR: This randomised phase III study compared the efficacy of O versus R in combination with DHAP, aiming to improve PFS following salvage treatment and ASCT, and found sAAIPI and response duration after first-line treatment were risk factors significantly associated with PFS and OS.
27 citations
TL;DR: Ofatumumab pharmacokinetics were well described by a linear two‐compartment model component to represent non‐specific monoclonal antibody clearance from the central compartment interacting with a model component representing the target‐mediated clearance of ofatumumabs by binding to CD20 expressed on B cells.
Abstract: Ofatumumab is a human monoclonal antibody directed at CD20 approved for treatment of chronic lymphocytic leukemia. The population pharmacokinetics of intravenous ofatumumab were characterized in patients with relapsed/refractory chronic lymphocytic leukemia, relapsed/refractory follicular lymphoma, and rheumatoid arthritis, diseases with widely varying CD20⁺ B-cell counts in blood. Serum concentration data from a total of 477 patients who received ofatumumab doses ranging from 100 mg to 2000 mg in different dosing regimens were analyzed to determine the pharmacokinetic characteristics of ofatumumab across different patient groups and to identify factors contributing to the pharmacokinetic variability. Ofatumumab pharmacokinetics were well described by a linear two-compartment model component to represent non-specific monoclonal antibody clearance from the central compartment interacting with a model component representing the target-mediated clearance of ofatumumab by binding to CD20 expressed on B cells. The clearance (7.5 mL/h) and steady-state volume of distribution (5.3 L) for the linear, non-specific component were consistent with results obtained for other monoclonal antibodies. The target-mediated clearance component was related to the disease-specific number of circulating B cells, which will allow simulation of the contribution of target-mediated clearance to ofatumumab pharmacokinetics in untested disease states with data on B-cell counts and turnover.
26 citations
Sarah Cannon Research Institute1, Stanford University2, University of British Columbia3, Fred Hutchinson Cancer Research Center4, Lyon College5, New York University6, Jewish General Hospital7, Huntsman Cancer Institute8, University of Amsterdam9, University of Bologna10, Georgetown University Medical Center11, Genentech12, Willamette University13
TL;DR: The current study aims to compare PoV and PiV + RTX in R/R DLBCL and R/ R follicular lymphoma (FL), with similar safety profiles of both regimens.
Abstract: 8519 Background: PoV and PiV, antibody drug conjugates (ADC) containing the anti-mitotic MMAE targeting CD79b (PoV) and CD22 (PiV), showed clinical activity in Phase I. The current study aims to compare PoV and PiV + RTX in R/R DLBCL and R/R follicular lymphoma (FL). Methods: Pts were randomized to receive PoV or PiV + RTX (ADC 2.4 mg/kg + RTX 375 mg/m2) every 21 days. Tumor assessments were performed every 3 months. Results: As of 8 November 2013, 58 received PoV + RTX (38 DLBCL; 20 FL), 63 PiV + RTX (42 DLBCL; 21 FL). Median prior therapies [DLBCL, 3 (1-10); FL, 2 (1-8)] were balanced between treatment arms; 46% were RTX refractory. Median treatment (tx) cycles in DLBCL: 5 for both ADC (1-15); FL: 8.5 PoV (3-15) and 6 PiV (1-13). Overall safety profiles of both regimens were similar. Tx-emergent adverse events (AE) >25%: fatigue (52%), diarrhea (42%), nausea (37%), peripheral neuropathy (PN) (32%), constipation (26%). Grade ≥ 3 AE >3%: neutropenia (21%), diarrhea (6%), dyspnea (4%), febrile neutropenia ...
25 citations