Cramer, Paula, Tausch, Eugen, von Tresckow, Julia, Giza, Adam, Robrecht, Sandra, Schneider, Christof, Furstenau, Moritz, Langerbeins, Petra, Al-Sawaf, Othman, Pelzer, Benedikt W., Fink, Anna Maria ORCID: 0000-0002-7669-7890, Fischer, Kirsten, Wendtner, Clemens-Martin, Eichhorst, Barbara, Kneba, Michael, Stilgenbauer, Stephan and Hallek, Michael (2021). Durable remissions following combined targeted therapy in patients with CLL harboring TP53 deletions and/or mutations. Blood, 138 (19). S. 1805 - 1817. WASHINGTON: AMER SOC HEMATOLOGY. ISSN 1528-0020

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Abstract

Fifty-one of 189 evaluable patients from 3 prospective phase 2 trials evaluating a sequential targeted treatment had high-risk chronic lymphocytic leukemia (CLL) with a 17p deletion, TP53 mutation, or both. Twenty-seven patients started treatment with bendamustine debulking before induction and maintenance treatment, which was ibrutinib/ofatumumab (IO) in 21 patients, ibrutinib/obinutuzumab (IG) in 13, and venetoclax/obinutuzumab (AG) in 17. The primary end point was overall response rate after 8 months of induction treatment, which was 81%, 100%, and 94% for IO, IG, and AG, respectively. Minimal residual disease (MRD) was undetectable (uMRD) in peripheral blood (<10(-4) by flow cytometry) in 0%, 23%, and 82% of patients, respectively. Median progression-free survival (PFS) was 45 months. Seventeen patients discontinued maintenance treatment due to uMRD: 9 progressed, 2 died without progression (median PFS, 28 months after discontinuation of treatment), and 6 remained in remission after a median observation time of 46 months (range, 6-47 months) after treatment discontinuation. Thus, MRD-guided fixed-duration therapies combining obinutuzumab with venetoclax or ibrutinib can induce deep and durable remissions in CLL patients with high-risk genetic lesions, which can persist after treatment discontinuation (due to a predefined fixed-duration or MRD-guided early termination). The median PFS was 45 months.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cramer, PaulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tausch, EugenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Tresckow, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giza, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robrecht, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furstenau, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langerbeins, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al-Sawaf, OthmanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pelzer, Benedikt W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, Anna MariaUNSPECIFIEDorcid.org/0000-0002-7669-7890UNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendtner, Clemens-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichhorst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kneba, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-594369
DOI: 10.1182/blood.2020010484
Journal or Publication Title: Blood
Volume: 138
Number: 19
Page Range: S. 1805 - 1817
Date: 2021
Publisher: AMER SOC HEMATOLOGY
Place of Publication: WASHINGTON
ISSN: 1528-0020
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; OPEN-LABEL; IBRUTINIB; VENETOCLAX; MULTICENTER; RESISTANCE; OUTCOMES; OBINUTUZUMAB; OFATUMUMABMultiple languages
HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59436

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