FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2991018082> ?p ?o ?g. }

• W2991018082 endingPage "844" @default.
• W2991018082 startingPage "844" @default.
• W2991018082 abstract "Background Chronic myelomonocytic leukemia (CMML) is an ultrarare stem cell disorder defined by the presence of monocytosis (≥1.0 G/l, ≥10%). Depending on white blood cell (WBC) count, CMML can be divided into a myelodysplastic (MD) (WBC ≤13 G/l) and a myeloproliferative (MP) variant (WBC &gt;13 G/l). Although hypomethylating agents (HMA) have been shown to prolong overall survival (OS) in MDS patients (pts) in prospective, randomized phase III trials, only 6-14 MD-CMML pts were included, and MP-CMML pts were excluded [Silverman 2002; Kantarjian 2006; Fenaux 2009]. EMA approval of azacitidine (AZA) in CMML is thus based on limited experience and restricted to MD-CMML with 10-29% bone marrow blasts (BMB), whereas decitabine (DAC) is not approved for treatment (trt) of CMML in the EU. Smaller analyses and single-arm trials of HMA in CMML exist [Wijermans 2008; Ades 2013; Pleyer 2014; Zeidan 2017; Duchmann 2018; Santini 2018; Coston 2019; Diamantopoulos 2019], but it is still unclear whether HMA provide a benefit in CMML (subgroups) compared with other trts. Aim Evaluate the impact of HMA and hydroxyurea (HU) trt on OS and time to next trt (TTNT). Methods Data were collected from 7 European study groups and 2 US MDS Centers of Excellence; database lock 27.05.19; Assign Data Management and Biostatistics GmbH performed statistical analyses with SAS® 9.3. Of 1657 CMML pts, only those who received trt (n=950), with documented WBC and BMB at 1st line, were included in these analyses (n=845, cohort 1). Pts were stratified according to the EMA approved AZA indication, and inclusion/exclusion criteria of the GFM-DAC-CMML trial assessing DAC +/- HU vs HU (NCT02214407) (diagnosis of CMML, no prior trt [except supportive care, erythropoietin or ≤6 weeks HU], WBC ≥13 G/l and ≥2 of the following: BMB ≥5%, clonal cytogenetic abnormality [other than -Y], hemoglobin &lt;10 g/dL, neutrophil count &gt;16 G/l, platelet count &lt;100 G/L, splenomegaly; pts with ECOG&gt;2 excluded) (n=486; cohort 2). Results In cohort 1, pts receiving HMA 1st line (n=375) had longer OS (19.8 vs 16.3 months [mo], P=0.0102) and TTNT (13.2 vs 6.7 mo, P=0.0001) than pts treated with non-HMA 1st line (n=470). Survival benefit was longer when comparing pts who received HMA (any time) (AZA [n=442], DAC [n=37], both [n=27]) with those that never received HMA (never HMA; n=339) (23.0 vs 13.0 mo, P&lt;0.0001). Median OS was longer for MD-CMML (n=294) vs MP-CMML pts (n=551) (25.5 vs 15.0 mo, P&lt;0.0001). OS was shorter for all pts with 1st line HU preceding any 2nd line trt (9.4 vs 19.6 mo; P&lt;0.0001; Fig A), for MP-CMML pts separately (8.7 vs 15.6 mo, P=0.0001), and for the subset with HU preceding 2nd line HMA (11.6 vs 19.8 mo; P=0.0016; Fig B). The following were significantly less common in pts treated with HMA vs those that were not: diagnosis in the pre-HMA era (8 vs 43%), MP-CMML (48 vs 66%), splenomegaly (27 vs 36%), ECOG≥2 (12 vs 24%), 1 trt line (43 vs 74%). WHO subtype, karyotype, transfusion dependence, LDH, CPSS score, AML transformation and therapy-related CMML were comparable between cohorts. HMA are not approved in the EU for CMML pts with &lt;10% BMB. In this subgroup (n=588), median OS was longer for MD-CMML vs MP-CMML (28.1 vs 17.0 mo, P&lt;0.0001) and for pts who received HMA vs never HMA (26.5 vs 14.8 mo, P=0.0003). Pts with &lt;10% BMB and MD-CMML (n=206) did not seem to benefit from HMA vs non-HMA trt (median OS 28.4 vs 25.3 mo, P=0.9908; Fig C), whereas the MP-CMML subgroup (n=382) did (24.4 vs 13.0 mo, P&lt;0.0001; Fig D). HMA are also unapproved in the EU for MP-CMML pts with ≥10% BMB. In pts with ≥10% BMB (n=257), median OS was longer for MD-CMML vs MP-CMML (19.4 vs 11.2 mo, P=0.0023) and for pts who received HMA vs never HMA (18.3 vs 7.0 mo, P&lt;0.0001). Both MD-CMML (OS 21.7 vs 10.9 mo, p=0.0134; Fig E) and MP-CMML pts (15.6 vs 6.3 mo, P&lt;0.0001; Fig F) benefited from HMA trt vs never HMA. In cohort 2, 1st line trts were HU (n=214), HMA (n=187) and others (n=85). Comparing HMA vs HU 1st line, median OS was 15.6 vs 14.5 mo (P=0.0307) and median TTNT was 8.8 vs 6.5 mo (P=0.0452; Fig G). OS and TTNT were comparable for HU vs other trts (Fig G). Similar observations were made in the larger cohort 1 (Fig H). Conclusions HMA show promising results with survival benefits of +11.4, +10.8 and +9.3 mo in pts with MP-CMML &lt;10%, and MD- or MP-CMML ≥10% BMB. In MP-CMML pts fulfilling GFM-DAC-CMML trial inclusion criteria, survival and TTNT were longest in pts receiving HMA 1st line as compared to HU or other trts. Preceding HU portends poor prognosis (-10.2 mo). Disclosures Pleyer: Abbvie: Other: Advisory board; Novartis: Other: Advisory board; Inflection Point Biomedical Advisors: Other: Advisory board; Celgene: Other: Advisory board; Agios: Other: Advisory board. Leisch:Novartis: Honoraria, Other: Travel support; Bristol-Myers-Squibb: Honoraria; Celgene: Other: Travel support. Maciejewski:Alexion: Consultancy; Novartis: Consultancy. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Heibl:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Roche: Honoraria; Daiichi Sankyo: Honoraria; Mundipharma: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AOP Orphan Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Geissler:Novartis: Honoraria; Roche: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria; AOP: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Ratiopharm: Honoraria. Valent:Blueprint: Research Funding; Pfizer: Honoraria; Deciphera: Honoraria, Research Funding; Celgene: Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Medina de Almeida:Novartis: Speakers Bureau; Celgene: Speakers Bureau. Jerez:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Germing:Novartis: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Symeonidis:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Tekeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sanz:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Helsinn Healthcare: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffman - La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen - Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Membership on an entity's Board of Directors or advisory committees, Research Funding. Greil:Boehringer Ingelheim: Honoraria; Amgen: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding; Janssen-Cilag: Honoraria; Mundipharma: Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Eisai: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel/accomodation expenses, Research Funding. OffLabel Disclosure: Azacitidine is not approved for the treatment of MP-CMML or CMML with &lt;10% BM blasts, decitabine is not approved for treatment of CMML in the EU, hydroxyurea is not approved for the treatment of CMML in the EU." @default.
• W2991018082 created "2019-12-05" @default.
• W2991018082 creator A5000552138 @default.
• W2991018082 creator A5003150190 @default.
• W2991018082 creator A5005172825 @default.
• W2991018082 creator A5006306448 @default.
• W2991018082 creator A5007988543 @default.
• W2991018082 creator A5010899085 @default.
• W2991018082 creator A5012199848 @default.
• W2991018082 creator A5014792758 @default.
• W2991018082 creator A5019954410 @default.
• W2991018082 creator A5020631581 @default.
• W2991018082 creator A5024960041 @default.
• W2991018082 creator A5025768647 @default.
• W2991018082 creator A5026573103 @default.
• W2991018082 creator A5032856028 @default.
• W2991018082 creator A5033064022 @default.
• W2991018082 creator A5034604940 @default.
• W2991018082 creator A5034834044 @default.
• W2991018082 creator A5036299617 @default.
• W2991018082 creator A5039994927 @default.
• W2991018082 creator A5041754278 @default.
• W2991018082 creator A5048355658 @default.
• W2991018082 creator A5052287429 @default.
• W2991018082 creator A5052934298 @default.
• W2991018082 creator A5053254720 @default.
• W2991018082 creator A5053284301 @default.
• W2991018082 creator A5055740968 @default.
• W2991018082 creator A5056386020 @default.
• W2991018082 creator A5057774263 @default.
• W2991018082 creator A5066001318 @default.
• W2991018082 creator A5067159029 @default.
• W2991018082 creator A5073037814 @default.
• W2991018082 creator A5074130459 @default.
• W2991018082 creator A5077151480 @default.
• W2991018082 creator A5078784112 @default.
• W2991018082 creator A5079390465 @default.
• W2991018082 creator A5079734282 @default.
• W2991018082 creator A5085974329 @default.
• W2991018082 creator A5086626929 @default.
• W2991018082 creator A5088353355 @default.
• W2991018082 date "2019-11-13" @default.
• W2991018082 modified "2023-10-17" @default.
• W2991018082 title "Effects of the Therapeutic Armamentarium on Survival and Time to Next Treatment in CMML Subtypes: An International Analysis of 950 Cases Coordinated By the AGMT Study Group" @default.
• W2991018082 doi "https://doi.org/10.1182/blood-2019-123941" @default.
• W2991018082 hasPublicationYear "2019" @default.
• W2991018082 type Work @default.
• W2991018082 sameAs 2991018082 @default.
• W2991018082 citedByCount "3" @default.
• W2991018082 countsByYear W29910180822020 @default.
• W2991018082 countsByYear W29910180822021 @default.
• W2991018082 crossrefType "journal-article" @default.
• W2991018082 hasAuthorship W2991018082A5000552138 @default.
• W2991018082 hasAuthorship W2991018082A5003150190 @default.
• W2991018082 hasAuthorship W2991018082A5005172825 @default.
• W2991018082 hasAuthorship W2991018082A5006306448 @default.
• W2991018082 hasAuthorship W2991018082A5007988543 @default.
• W2991018082 hasAuthorship W2991018082A5010899085 @default.
• W2991018082 hasAuthorship W2991018082A5012199848 @default.
• W2991018082 hasAuthorship W2991018082A5014792758 @default.
• W2991018082 hasAuthorship W2991018082A5019954410 @default.
• W2991018082 hasAuthorship W2991018082A5020631581 @default.
• W2991018082 hasAuthorship W2991018082A5024960041 @default.
• W2991018082 hasAuthorship W2991018082A5025768647 @default.
• W2991018082 hasAuthorship W2991018082A5026573103 @default.
• W2991018082 hasAuthorship W2991018082A5032856028 @default.
• W2991018082 hasAuthorship W2991018082A5033064022 @default.
• W2991018082 hasAuthorship W2991018082A5034604940 @default.
• W2991018082 hasAuthorship W2991018082A5034834044 @default.
• W2991018082 hasAuthorship W2991018082A5036299617 @default.
• W2991018082 hasAuthorship W2991018082A5039994927 @default.
• W2991018082 hasAuthorship W2991018082A5041754278 @default.
• W2991018082 hasAuthorship W2991018082A5048355658 @default.
• W2991018082 hasAuthorship W2991018082A5052287429 @default.
• W2991018082 hasAuthorship W2991018082A5052934298 @default.
• W2991018082 hasAuthorship W2991018082A5053254720 @default.
• W2991018082 hasAuthorship W2991018082A5053284301 @default.
• W2991018082 hasAuthorship W2991018082A5055740968 @default.
• W2991018082 hasAuthorship W2991018082A5056386020 @default.
• W2991018082 hasAuthorship W2991018082A5057774263 @default.
• W2991018082 hasAuthorship W2991018082A5066001318 @default.
• W2991018082 hasAuthorship W2991018082A5067159029 @default.
• W2991018082 hasAuthorship W2991018082A5073037814 @default.
• W2991018082 hasAuthorship W2991018082A5074130459 @default.
• W2991018082 hasAuthorship W2991018082A5077151480 @default.
• W2991018082 hasAuthorship W2991018082A5078784112 @default.
• W2991018082 hasAuthorship W2991018082A5079390465 @default.
• W2991018082 hasAuthorship W2991018082A5079734282 @default.
• W2991018082 hasAuthorship W2991018082A5085974329 @default.
• W2991018082 hasAuthorship W2991018082A5086626929 @default.
• W2991018082 hasAuthorship W2991018082A5088353355 @default.
• W2991018082 hasBestOaLocation W29910180821 @default.
• W2991018082 hasConcept C126322002 @default.
• W2991018082 hasConcept C143998085 @default.
• W2991018082 hasConcept C71924100 @default.
• W2991018082 hasConceptScore W2991018082C126322002 @default.
• W2991018082 hasConceptScore W2991018082C143998085 @default.
• W2991018082 hasConceptScore W2991018082C71924100 @default.

• next