Quantitative Analysis of Minimal Residual Disease (MRD) Shows High Rates of Undetectable MRD after Fixed-Duration Chemotherapy-Free Treatment and Serves As Surrogate Marker for Progression-Free Survival: A Prospective Analysis of the Randomized CLL14 Trial

Autor: Sebastian Böttcher, Yanwen Jiang, Monika Brüggemann, Othman Al-Sawaf, Anton W. Langerak, Matthias Ritgen, Anna-Maria Fink, Barbara Eichhorst, Maneesh Tandon, Anke Schilhabel, Kirsten Fischer, William Schary, Michael Hallek, Michael Kneba, Clemens-Martin Wendtner, Eugen Tausch, Stephan Stilgenbauer, Thomas Stübig, Karl-Anton Kreuzer, Sandra Robrecht, Valentin Goede
Přispěvatelé: Immunology
Rok vydání: 2019
Předmět:
Zdroj: Blood, 134(1). American Society of Hematology
ISSN: 1528-0020
0006-4971
Popis: Purpose Although minimal residual disease (MRD) is an established surrogate marker for outcomes following treatment with chemoimmunotherapy, less is known about the value of MRD in chemotherapy-free treatments in the first-line setting. We investigated the prognostic value of MRD detection after a fixed-duration treatment of venetoclax plus obinutuzumab (VenG) with respect to clinical and genetic risk factors and source of material in previously untreated patients (pts) with CLL and coexisting conditions. Methods In this multinational, open-label, Phase 3 trial, 432 previously untreated pts with a Cumulative Illness Rating Scale score >6 and/or an estimated creatinine clearance Results On the basis of the intention-to-treat population (i.e. for the full trial population and irrespective of sample availability), VenG achieved higher rates of undetectable MRD at EOT compared with chlorambucil and obinutuzumab (ClbG) (PB: 75.5% vs. 35.2%, BM: 56.9% vs. 17.1%). In contrast, detectable MRD in PB was found in 19 (8.8%) VenG pts and 103 (47.7%) ClbG pts. Of these, 11 (5.1%) VenG vs. 47 (21.8%) ClbG pts had intermediate MRD at ≥10-4- Conclusion Fixed-duration treatment with VenG achieves unprecedentedly high and sustainable rates of undetectable MRD in patients with previously untreated CLL and coexisting conditions. Findings confirm the prognostic value of MRD assessment at EOT for this chemotherapy-free treatment regimen. Due to high concordance of undetectable MRD in PB and BM in the context of VenG, BM assessments may not be required for these patients. Disclosures Fischer: Roche: Other: travel grants; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ritgen:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding. Al-Sawaf:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel support; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Tandon:Roche: Equity Ownership; Roche Products Ltd: Employment. Fink:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Roche: Other: travel grants. Stübig:Hexal: Speakers Bureau. Brüggemann:Amgen, Celgene, Janssen: Honoraria, Speakers Bureau; Amgen, Janssen: Membership on an entity's Board of Directors or advisory committees; affimed, Amgen, Celgene, Regeneron: Research Funding; Amgen, Incyte, PRMA: Consultancy. Jiang:Genentech: Employment, Equity Ownership; F. Hoffman-La Roche: Equity Ownership. Schary:Abbvie: Employment, Equity Ownership. Eichhorst:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BeiGene: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ArQule: Membership on an entity's Board of Directors or advisory committees. Wendtner:MorphoSys: Consultancy, Honoraria, Research Funding; GILEAD Science: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen-CILAG: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding. Tausch:AbbVie: Consultancy, Honoraria, Other: travel support, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau. Kreuzer:Roche and Abbvie: Honoraria, Other: Expert testimony. Langerak:F. Hoffmann-La Roche Ltd: Research Funding; Gilead: Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Genentech, Inc.: Research Funding. Goede:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants, speaker fees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: speaker fees, Speakers Bureau; janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants, speaker fees, Speakers Bureau. Böttcher:AbbVie: Honoraria, Other: Travel grants, Research Funding; Celgene: Research Funding; Janssen-CILAG: Honoraria, Other: Travel grants, Research Funding; Roche: Honoraria, Research Funding; Genentech: Research Funding; Becton Dickinson: Research Funding; Novartis: Research Funding. Stilgenbauer:AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Other: Travel support; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Hoffmann La-Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Hallek:Roche, Gilead Sciences, Inc., Mundipharma, Janssen, Celgene, Pharmacyclics, AbbVie: Honoraria, Research Funding, Speakers Bureau.
Databáze: OpenAIRE
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