Kater, Arnon P., Wu, Jenny Qun, Kipps, Thomas, Eichhorst, Barbara, Hillmen, Peter ORCID: 0000-0001-5617-4403, D'Rozario, James, Assouline, Sarit ORCID: 0000-0002-7638-1589, Owen, Carolyn, Robak, Tadeusz, de la Serna, Javier, Jaeger, Ulrich, Cartron, Guillaume, Montillo, Marco, Dubois, Julie, Eldering, Eric, Mellink, Clemens, Van Der Kevie-Kersemaekers, Anne-Marie, Kim, Su Young, Chyla, Brenda, Punnoose, Elizabeth, Bolen, Christopher R., Assaf, Zoe June, Jiang, Yanwen, Wang, Jue, Lefebure, Marcus, Boyer, Michelle, Humphrey, Kathryn and Seymour, John F. (2020). Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study. J. Clin. Oncol., 38 (34). ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

PURPOSEIn previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics.PATIENTS AND METHODSPatients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed.RESULTSOf 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC (P = .042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with BIRC3 and BRAF mutations at EOCT and with TP53, NOTCH1, XPO1, and BRAF mutations at EOT.CONCLUSIONEfficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kater, Arnon P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Jenny QunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kipps, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichhorst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillmen, PeterUNSPECIFIEDorcid.org/0000-0001-5617-4403UNSPECIFIED
D'Rozario, JamesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assouline, SaritUNSPECIFIEDorcid.org/0000-0002-7638-1589UNSPECIFIED
Owen, CarolynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robak, TadeuszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de la Serna, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaeger, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cartron, GuillaumeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montillo, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dubois, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eldering, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mellink, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Der Kevie-Kersemaekers, Anne-MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Su YoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chyla, BrendaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Punnoose, ElizabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolen, Christopher R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assaf, Zoe JuneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, YanwenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lefebure, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boyer, MichelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Humphrey, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seymour, John F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-310005
DOI: 10.1200/JCO.20.00948
Journal or Publication Title: J. Clin. Oncol.
Volume: 38
Number: 34
Date: 2020
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CLL; BENDAMUSTINE; PROGRESSION; EVOLUTION; FRAMEWORKMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31000

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