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Title: | Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. | Authors: | Kreuzer K.-A.;Hallek M.;Langerak A.W.;Ritgen M.;Mobasher M.;Stilgenbauer S.;Goede V.;Fischer K.;Al-Sawaf O.;Bahlo J.;Fink A.-M.;Tandon M.;Dixon M.;Robrecht S.;Warburton S.;Humphrey K.;Samoylova O.;Liberati A.M.;Pinilla-Ibarz J.;Opat S. ;Sivcheva L.;Le Du K.;Fogliatto L.M.;Niemann C.U.;Weinkove R.;Robinson S.;Kipps T.J.;Boettcher S.;Tausch E.;Humerickhouse R.;Eichhorst B.;Wendtner C.-M. | Institution: | (Fischer, Al-Sawaf, Bahlo, Fink, Robrecht, Eichhorst, Kreuzer, Hallek) Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Kerpener Str. 62, Cologne 50937, Germany (Goede) Oncogeriatric Unit, Department of Geriatric Medicine, St. Marien Hospital, Germany (Hallek) CECAD (Center of Excellence on Cellular Stress Responses in Aging-Assoc. Diseases, Germany (Hallek) Center for Molecular Medicine Cologne, Cologne, Germany (Boettcher) Department III of Internal Medicine, University Hospital Rostock, Rostock, Germany (Tausch, Stilgenbauer) Department III of Internal Medicine, Ulm University, Ulm, Germany (Wendtner) Departments of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases, Klinikum Schwabing, Munich, Germany (Ritgen) Department II of Internal Medicine, Campus Kiel, University of Schleswig-Holstein, Kiel, Germany (Stilgenbauer) Department of Hematology, Oncology, and Rheumatology, Saarland University Medical School, Homburg, Germany (Tandon, Dixon, Warburton, Humphrey, Mobasher) Roche Products, Welwyn Garden City, United Kingdom (Samoylova) Regional Clinical Hospital N.A. Semashko, Nizhny Novgorod, Russian Federation (Liberati) Division of Onco-Hematology, Santa Maria Terni Hospital, University of Perugia, Perugia, Italy (Pinilla-Ibarz) Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States (Opat) Haematology Department, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia (Sivcheva) First Internal Department, Multiprofile Hospital for Active Treatment Hristo Botev, Vratsa, Bulgaria (Le Du) Hematology Department, Clinique Victor Hugo, Le Mans, France (Fogliatto) Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (Niemann) Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (Weinkove) Wellington Blood and Cancer Centre, Capital and Coast District Health Board, Malaghan Institute of Medical Research, Wellington, New Zealand (Robinson) Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada (Kipps) Moores Cancer Center, University of California San Diego, San Diego, CA, United States (Mobasher) Genentech, South San Francisco, CA, United States (Humerickhouse) AbbVie, North Chicago, IL, United States (Langerak) Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, Netherlands | Issue Date: | 17-Jun-2019 | Copyright year: | 2019 | Publisher: | Massachussetts Medical Society | Place of publication: | United States | Publication information: | New England Journal of Medicine. 380 (23) (pp 2225-2236), 2019. Date of Publication: 06 Jun 2019. | Journal: | New England Journal of Medicine | Abstract: | Background: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known. Method(s): In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil- obinutuzumab. The primary end point was investigator-assessed progression- free survival. The safety of each regimen was also evaluated. Result(s): In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression- free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax- obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant. Conclusions Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil- obinutuzumab.Copyright © 2019 Massachusetts Medical Society. | DOI: | http://monash.idm.oclc.org/login?url=http://acs.hcn.com.au/?acc=36265&url=http://dx.doi.org/10.1056/NEJMoa1815281 | PubMed URL: | 31166681 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31166681] | ISSN: | 0028-4793 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/35653 | Type: | Article | Subjects: | creatinine/ec [Endogenous Compound] aged all cause mortality article cancer growth cancer mortality cancer survival *chronic lymphatic leukemia/dt [Drug Therapy] clinical article creatinine clearance drug safety female follow up gene gene deletion gene mutation human infection/si [Side Effect] male neutropenia/si [Side Effect] open study phase 3 clinical trial priority journal progression free survival rating scale scoring system treatment duration *chlorambucil/ae [Adverse Drug Reaction] *chlorambucil/ct [Clinical Trial] *chlorambucil/cb [Drug Combination] *chlorambucil/dt [Drug Therapy] *obinutuzumab/ae [Adverse Drug Reaction] *obinutuzumab/ct [Clinical Trial] *obinutuzumab/cb [Drug Combination] *obinutuzumab/dt [Drug Therapy] *venetoclax/ae [Adverse Drug Reaction] *venetoclax/ct [Clinical Trial] *venetoclax/cb [Drug Combination] *venetoclax/dt [Drug Therapy] TP53 gene creatinine clearance drug safety female follow up gene gene deletion gene mutation human male neutropenia / side effect open study phase 3 clinical trial priority journal progression free survival rating scale scoring system treatment duration infection / side effect aged all cause mortality Article cancer growth cancer mortality cancer survival *chronic lymphatic leukemia / *drug therapy clinical article |
Type of Clinical Study or Trial: | Clinical trial |
Appears in Collections: | Articles |
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