Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab.

Autor:	Seymour JF; Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia., Kipps TJ; UCSD Moores Cancer Center, San Diego, CA., Eichhorst BF; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine and Center of Integrated Oncology Aachen, Bonn, Cologne, Dusseldorf (CIO ABCD), Cologne, Germany., D'Rozario J; The John Curtin School of Medical Research, Australian National University, Canberra, Australia., Owen CJ; University of Calgary, Calgary, AB, Canada., Assouline S; Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada., Lamanna N; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY., Robak T; Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland., de la Serna J; Hospital Universitario 12 de Octubre, Madrid, Spain., Jaeger U; Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria., Cartron G; Department of Hematology, Centre Hospitalier Universitaire de Montpellier (UMR-CNRS 5535), Montpellier, France., Montillo M; Department of Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Mellink C; Department of Human Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Chyla B; AbbVie, North Chicago, IL., Panchal A; Roche Products Ltd., Welwyn Garden City, United Kingdom., Lu T; Genentech, Inc., South San Francisco, CA; and., Wu JQ; Genentech, Inc., South San Francisco, CA; and., Jiang Y; Genentech, Inc., South San Francisco, CA; and., Lefebure M; Roche Products Ltd., Welwyn Garden City, United Kingdom., Boyer M; Roche Products Ltd., Welwyn Garden City, United Kingdom., Kater AP; Department of Hematology, Cancer Center Amsterdam, Lymphoma and Myeloma Center Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2022 Aug 25; Vol. 140 (8), pp. 839-850.
DOI:	10.1182/blood.2021015014
Abstrakt:	The MURANO trial (A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia [CLL]; ClinicalTrials.gov identifier #NCT02005471) reported superior progression-free survival (PFS) and overall survival (OS) with venetoclax-rituximab (VenR) vs bendamustine-rituximab (BR) in relapsed/refractory (R/R) CLL. Patients were randomized to 2 years of VenR (n = 194; rituximab for the first 6 months) or 6 months of BR (n = 195). Although undetectable minimal residual disease (uMRD) was achieved more often with VenR, the long-term implications of uMRD with this fixed-duration, chemotherapy-free regimen have not been explored. We report MRD kinetics and updated outcomes with 5 years' follow-up. Survival benefits with VenR vs BR were sustained (median PFS [95% confidence interval]: 53.6 [48.4, 57.0] vs 17.0 [15.5, 21.7] months, respectively, P < .0001; 5-year OS [95% confidence interval]: 82.1% [76.4, 87.8] vs 62.2% [54.8, 69.6], P < .0001). VenR was superior to BR, regardless of cytogenetic category. VenR-treated patients with uMRD at end of treatment (EOT; n = 83) had superior OS vs those with high-MRD+ (n = 12): 3-year post-EOT survival rates were 95.3% vs 72.9% (P = .039). In those with uMRD at EOT, median time to MRD conversion was 19.4 months. Of 47 patients with documented MRD conversion, 19 developed progressive disease (PD); median time from conversion to PD was 25.2 months. A population-based logistic growth model indicated slower MRD median doubling time post-EOT with VenR (93 days) vs BR (53 days; P = 1.2 × 10-7). No new safety signals were identified. Sustained survival, uMRD benefits, and durable responses support 2-year fixed-duration VenR treatment in R/R CLL. (© 2022 by The American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu