FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385647566> ?p ?o ?g. }

• W4385647566 endingPage "e26114b3" @default.
• W4385647566 startingPage "e26114b3" @default.
• W4385647566 abstract "Background: Venetoclax-based therapy is a standard option for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) previously treated with a covalent BTK inhibitor (cBTKi). However, nearly all prospective data on venetoclax efficacy in the post-cBTKi setting were generated from a subgroup analysis within a single-arm study of venetoclax administered as continuous monotherapy. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that was designed to overcome the pharmacologic limitations of cBTKi and restore BTK inhibition. Pirtobrutinib has demonstrated marked efficacy and a favorable safety profile in patients with CLL previously treated with a cBTKi. Aims: This unanchored MAIC was designed to estimate the treatment effect of pirtobrutinib (BRUIN, NCT03740529) versus venetoclax continuous monotherapy (NCT02141282) in patients with R/R CLL previously treated with a cBTKi. Methods: Data from patients with R/R CLL previously treated with at least one cBTKi and without prior venetoclax exposure who received pirtobrutinib were analyzed (n=146). Only one prospective trial of venetoclax (administered as a continuous monotherapy) for patients previously treated with a cBTKi (n=91) was identified (Jones et al., 2018). Progression-free survival (PFS), overall survival (OS), investigator-assessed overall response rate (ORR), and grade ≥3 treatment-emergent adverse events (TEAEs) regardless of attribution were evaluated. Patient level data from the pirtobrutinib cohort were re-weighted to match the venetoclax cohort using method of moments approach, adjusting for well-established prognostic factors reported in both studies (age, IGHV mutation status, TP53 aberrancy, del(17p), del(11q); number of prior lines of therapy, and reason for prior cBTKi discontinuation). Kaplan Meier PFS and OS curves from the venetoclax trial were digitized (using WebPlotDigitizer) for time-to-event analyses. Fishers exact test was used to compare proportional outcomes (ORR, TEAEs); time to event outcomes (PFS, OS) were compared using Cox regression model and log-rank test. Results: After adjustment, the median age in the pirtobrutinib and venetoclax cohorts was 66.5 and 66.0 years, respectively; all other prognostic factors were similarly well matched in both cohorts. Median follow-up was 21.3 months and 14 months for the pirtobrutinib and venetoclax cohorts, respectively. PFS and OS were comparable with no significant differences noted for pirtobrutinib versus venetoclax (both p>0.05; Figure). ORR was 80% for pirtobrutinib (inclusive of PR-L) vs 65% for venetoclax (p=0.01). Grade ≥3 TEAEs reported in both trials indicated that febrile neutropenia, neutropenia, anemia, and thrombocytopenia were significantly lower for pirtobrutinib vs venetoclax in adjusted analyses (all p<0.01). No differences were observed for pneumonia (p=0.06) or for discontinuation due to TEAEs (3% vs 7%, p=0.32) in adjusted analyses. Unadjusted results were consistent with the adjusted analyses. Summary/Conclusion: The efficacy of pirtobrutinib was comparable to continuously administered venetoclax monotherapy in patients with R/R CLL previously treated with a cBTKi. Pirtobrutinib was associated with improved ORR and favorable overall safety profile for most TEAEs compared to venetoclax. This study raises questions regarding optimal treatment sequencing of pirtobrutinib and venetoclax in cBTKi treated CLL, but the lack of prospective direct comparisons and limited long-term follow-up preclude definitive conclusions. Multiple randomized Phase 3 studies of pirtobrutinib in patients with CLL remain ongoing.Keywords: Chronic lymphocytic leukemia" @default.
• W4385647566 created "2023-08-09" @default.
• W4385647566 creator A5018460766 @default.
• W4385647566 creator A5037225193 @default.
• W4385647566 creator A5040412322 @default.
• W4385647566 creator A5053298824 @default.
• W4385647566 creator A5056742611 @default.
• W4385647566 creator A5071015984 @default.
• W4385647566 creator A5085633786 @default.
• W4385647566 date "2023-08-01" @default.
• W4385647566 modified "2023-09-27" @default.
• W4385647566 title "P623: MATCHING-ADJUSTED INDIRECT COMPARISON (MAIC) OF PIRTOBRUTINIB VS VENETOCLAX CONTINUOUS MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY CLL PREVIOUSLY TREATED WITH A COVALENT BTK INHIBITOR" @default.
• W4385647566 doi "https://doi.org/10.1097/01.hs9.0000969396.26114.b3" @default.
• W4385647566 hasPublicationYear "2023" @default.
• W4385647566 type Work @default.
• W4385647566 citedByCount "0" @default.
• W4385647566 crossrefType "journal-article" @default.
• W4385647566 hasAuthorship W4385647566A5018460766 @default.
• W4385647566 hasAuthorship W4385647566A5037225193 @default.
• W4385647566 hasAuthorship W4385647566A5040412322 @default.
• W4385647566 hasAuthorship W4385647566A5053298824 @default.
• W4385647566 hasAuthorship W4385647566A5056742611 @default.
• W4385647566 hasAuthorship W4385647566A5071015984 @default.
• W4385647566 hasAuthorship W4385647566A5085633786 @default.
• W4385647566 hasBestOaLocation W43856475661 @default.
• W4385647566 hasConcept C121332964 @default.
• W4385647566 hasConcept C126322002 @default.
• W4385647566 hasConcept C142424586 @default.
• W4385647566 hasConcept C143998085 @default.
• W4385647566 hasConcept C2777609679 @default.
• W4385647566 hasConcept C2777938653 @default.
• W4385647566 hasConcept C2778461978 @default.
• W4385647566 hasConcept C2779675984 @default.
• W4385647566 hasConcept C71924100 @default.
• W4385647566 hasConcept C87355193 @default.
• W4385647566 hasConcept C90924648 @default.
• W4385647566 hasConceptScore W4385647566C121332964 @default.
• W4385647566 hasConceptScore W4385647566C126322002 @default.
• W4385647566 hasConceptScore W4385647566C142424586 @default.
• W4385647566 hasConceptScore W4385647566C143998085 @default.
• W4385647566 hasConceptScore W4385647566C2777609679 @default.
• W4385647566 hasConceptScore W4385647566C2777938653 @default.
• W4385647566 hasConceptScore W4385647566C2778461978 @default.
• W4385647566 hasConceptScore W4385647566C2779675984 @default.
• W4385647566 hasConceptScore W4385647566C71924100 @default.
• W4385647566 hasConceptScore W4385647566C87355193 @default.
• W4385647566 hasConceptScore W4385647566C90924648 @default.
• W4385647566 hasIssue "S3" @default.
• W4385647566 hasLocation W43856475661 @default.
• W4385647566 hasLocation W43856475662 @default.
• W4385647566 hasOpenAccess W4385647566 @default.
• W4385647566 hasPrimaryLocation W43856475661 @default.
• W4385647566 hasRelatedWork W2204827588 @default.
• W4385647566 hasRelatedWork W2894684271 @default.
• W4385647566 hasRelatedWork W2902590192 @default.
• W4385647566 hasRelatedWork W2952202744 @default.
• W4385647566 hasRelatedWork W2982731272 @default.
• W4385647566 hasRelatedWork W3025337836 @default.
• W4385647566 hasRelatedWork W3116010448 @default.
• W4385647566 hasRelatedWork W4308968203 @default.
• W4385647566 hasRelatedWork W4379768976 @default.
• W4385647566 hasRelatedWork W4382929662 @default.
• W4385647566 hasVolume "7" @default.
• W4385647566 isParatext "false" @default.
• W4385647566 isRetracted "false" @default.
• W4385647566 workType "article" @default.