FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3097090129> ?p ?o ?g. }

• W3097090129 endingPage "25" @default.
• W3097090129 startingPage "23" @default.
• W3097090129 abstract "Introduction Early identification of patients (pts) with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) at high risk for treatment failure may allow for interventions to improve outcomes; however, known prognostic factors are inadequate. Circulating tumor DNA (ctDNA) has demonstrated the ability to identify previously untreated DLBCL pts at high risk of relapse (Kurtz et al. 2018). We assessed the potential for ctDNA to identify pts with R/R DLBCL receiving bendamustine and rituximab (BR) +/- polatuzumab (pola) at higher risk for disease progression. Methods GO29365 (NCT02257567) is a Phase Ib/II study comparing pola+BR versus BR in pts with transplant-ineligible R/R DLBCL and enrolled 80 pts (n=40 per randomized arm). The primary efficacy objective was independent review committee (IRC)-assessed complete response (CR) rate at primary response assessment (PRA, 6-8 weeks after Cycle 6, Day 1 or last dose of study drug). ctDNA was measured in available cohort samples using a customized DLBCL panel on a modified ctDNA CAPP-Seq workflow developed based on the prototype assay reported in Kurtz et al. 2018, with improvement of sensitivity and specificity. ctDNA was reported as mean mutant molecules per mL (MMPM). Plasma depleted whole blood from baseline was used as a source of germline DNA to filter non-tumor-specific variants. A total of 43 samples were available at baseline; eight pts without a paired germline were excluded from efficacy and correlative analyses. Of the 35 samples (n=21 Pola+BR; n=14 BR) with available germline data, paired samples were available for 25 pts at PRA. Detectable ctDNA (+/-) was determined using empirical p-values (&lt;0.05) through a bootstrap algorithm (Newman et al. 2014, Pati et al. 2018). The proportions of pts with detectable ctDNA are reported by visit with 95% Clopper-Pearson binomial confidence intervals (CI). A Kruskal-Wallis test was used to compare ctDNA levels by response. Univariate and multivariate cox regression was used to correlate ctDNA levels with progression-free survival (PFS) and overall survival (OS). Results are reported descriptively without multiple testing correction. Results Intent-to-treat and biomarker evaluable populations were similar in demographics and efficacy, but there was a higher proportion of pola+BR versus BR pts assayed (60% vs 40%). Analyses are reported for the pooled arms, but results were consistent across both arms. ctDNA was detected in all available baseline (n=43) samples (95% CI: 92-100). Baseline ctDNA levels were correlated with known prognostic factors including International Prognostic Index (IPI), lactate dehydrogenase (LDH), Ann Arbor stage and number of prior therapies (Figure 1A). Higher ctDNA levels at baseline were negatively prognostic; when stratifying pts by median ctDNA levels the hazard ratio (HR) for PFS was 0.16 (95% CI: 0.07-0.41; Figure 1B); OS HR 0.23 (95% CI: 0.10-0.52). Similar results were observed for other quartile stratifications. This significant trend was maintained when adjusted in multivariate analysis for treatment, IPI &gt;3, and LDH &gt; upper limit of normal with an adjusted HR for PFS of 0.24 (95% CI: 0.07-0.81) and for OS an adjusted HR of 0.30 (95% CI: 0.09-0.97). Similar to the first-line setting (Kurtz et al. 2018), on-treatment log fold-changes in ctDNA trended with PRA response (Figure 1C); pts with a CR had a significantly greater average decrease in MMPM across timepoints than non-CR pts (Wilcoxon p-value &lt;0.001). At PRA, four pts (three in pola+BR, one in BR) had cleared ctDNA, potentially due to treatment, all of which achieved CR. ctDNA was detectable in the remaining patients (n=25, 84%, 95% CI: 64-95). There was no clear trend between log fold reduction of ctDNA at PRA and PFS in this cohort, though this analysis is limited by sample size. Conclusions Baseline ctDNA levels were correlated with standard clinical risk factors, and were shown to have independent prognostic value for response, PFS and OS in R/R DLBCL pts treated with BR +/- pola. The degree of ctDNA change upon treatment was also correlated with response, but association with PFS needs further investigation with a larger sample size. This provides early evidence that ctDNA can be used to improve identification of R/R DLBCL pts at high risk for disease progression/relapse. Figure Disclosures Herrera: AstraZeneca: Research Funding; Karyopharm: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Tracy:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Croft:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Opat:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZenca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Epizyme: Research Funding; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ray:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Musick:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Roche/Genentech, Inc.: Current Employment. Paulson:F. Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Sehn:Chugai: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Genentech, Inc.: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Verastem Oncology: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria. Jiang:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment." @default.
• W3097090129 created "2020-11-09" @default.
• W3097090129 creator A5019218337 @default.
• W3097090129 creator A5026641386 @default.
• W3097090129 creator A5030788778 @default.
• W3097090129 creator A5034453175 @default.
• W3097090129 creator A5063137777 @default.
• W3097090129 creator A5077150302 @default.
• W3097090129 creator A5079235139 @default.
• W3097090129 creator A5090258495 @default.
• W3097090129 creator A5091136841 @default.
• W3097090129 date "2020-11-05" @default.
• W3097090129 modified "2023-09-30" @default.
• W3097090129 title "Risk Profiling of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients By Measuring Circulating Tumor DNA" @default.
• W3097090129 doi "https://doi.org/10.1182/blood-2020-136645" @default.
• W3097090129 hasPublicationYear "2020" @default.
• W3097090129 type Work @default.
• W3097090129 sameAs 3097090129 @default.
• W3097090129 citedByCount "0" @default.
• W3097090129 crossrefType "journal-article" @default.
• W3097090129 hasAuthorship W3097090129A5019218337 @default.
• W3097090129 hasAuthorship W3097090129A5026641386 @default.
• W3097090129 hasAuthorship W3097090129A5030788778 @default.
• W3097090129 hasAuthorship W3097090129A5034453175 @default.
• W3097090129 hasAuthorship W3097090129A5063137777 @default.
• W3097090129 hasAuthorship W3097090129A5077150302 @default.
• W3097090129 hasAuthorship W3097090129A5079235139 @default.
• W3097090129 hasAuthorship W3097090129A5090258495 @default.
• W3097090129 hasAuthorship W3097090129A5091136841 @default.
• W3097090129 hasConcept C121608353 @default.
• W3097090129 hasConcept C126322002 @default.
• W3097090129 hasConcept C142424586 @default.
• W3097090129 hasConcept C142724271 @default.
• W3097090129 hasConcept C143998085 @default.
• W3097090129 hasConcept C2778559949 @default.
• W3097090129 hasConcept C2779338263 @default.
• W3097090129 hasConcept C2781335228 @default.
• W3097090129 hasConcept C502942594 @default.
• W3097090129 hasConcept C71924100 @default.
• W3097090129 hasConcept C86803240 @default.
• W3097090129 hasConcept C87355193 @default.
• W3097090129 hasConceptScore W3097090129C121608353 @default.
• W3097090129 hasConceptScore W3097090129C126322002 @default.
• W3097090129 hasConceptScore W3097090129C142424586 @default.
• W3097090129 hasConceptScore W3097090129C142724271 @default.
• W3097090129 hasConceptScore W3097090129C143998085 @default.
• W3097090129 hasConceptScore W3097090129C2778559949 @default.
• W3097090129 hasConceptScore W3097090129C2779338263 @default.
• W3097090129 hasConceptScore W3097090129C2781335228 @default.
• W3097090129 hasConceptScore W3097090129C502942594 @default.
• W3097090129 hasConceptScore W3097090129C71924100 @default.
• W3097090129 hasConceptScore W3097090129C86803240 @default.
• W3097090129 hasConceptScore W3097090129C87355193 @default.
• W3097090129 hasIssue "Supplement 1" @default.
• W3097090129 hasLocation W30970901291 @default.
• W3097090129 hasOpenAccess W3097090129 @default.
• W3097090129 hasPrimaryLocation W30970901291 @default.
• W3097090129 hasRelatedWork W1563073167 @default.
• W3097090129 hasRelatedWork W2026185605 @default.
• W3097090129 hasRelatedWork W2056936324 @default.
• W3097090129 hasRelatedWork W2098045335 @default.
• W3097090129 hasRelatedWork W2393199640 @default.
• W3097090129 hasRelatedWork W2507214293 @default.
• W3097090129 hasRelatedWork W2886448606 @default.
• W3097090129 hasRelatedWork W3001698141 @default.
• W3097090129 hasRelatedWork W3008207576 @default.
• W3097090129 hasRelatedWork W3215795316 @default.
• W3097090129 hasVolume "136" @default.
• W3097090129 isParatext "false" @default.
• W3097090129 isRetracted "false" @default.
• W3097090129 magId "3097090129" @default.
• W3097090129 workType "article" @default.