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Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group
Y. Herishanu, A. Shaulov, R. Fineman, S. Bašić-Kinda, A. Aviv, E. Wasik-Szczepanek, O. Jaksic, M. Zdrenghea, U. Greenbaum, I. Mandac, M. Simkovic, M. Morawska, O. Benjamini, M. Spacek, A. Nemets, O. Bairey, L. Trentin, R. Ruchlemer, L. Laurenti,...
Language English Country United States
Document type Clinical Trial, Journal Article, Multicenter Study, Observational Study
NLK
Free Medical Journals
from 1998 to 1 year ago
Wiley Free Content
from 1996 to 1 year ago
PubMed
32096887
DOI
10.1002/ajh.25766
Knihovny.cz E-resources
- MeSH
- Chlorambucil administration & dosage adverse effects MeSH
- Chromosome Deletion * MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * drug therapy genetics mortality MeSH
- Antibodies, Monoclonal, Humanized administration & dosage adverse effects MeSH
- Humans MeSH
- Chromosomes, Human, Pair 17 genetics MeSH
- Survival Rate MeSH
- Tumor Suppressor Protein p53 genetics MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Multicenter Study MeSH
- Observational Study MeSH
In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.
Barzilai University Medical Center Ashkelon Israel
Ben Gurion University Soroka University Medical Center Beer Sheva Israel
Charles University and General Hospital Prague Prague Czech Republic
Clinical Hospital Merkur Zagreb Croatia
Coltea Clinical Hospital Bucharest Romania
Department Hematology Oncology Azienda Ospedaliera Pugliese Ciaccio Catanzaro Italy
Department of Hematology Rambam Health Care Campus Haifa Israel
Department of Hematology Shaare Zedek Medical Center Jerusalem Israel
Department of Hematology Tel Aviv Sourasky Medical Center Tel Aviv Israel
Department of Hematooncology and Bone Marrow Transplantation Medical University Lublin Poland
Department of Molecular Biotechnology and Health Sciences University of Torino Torino Italy
Division of Hematology Cantonal Hospital of Lucerne Lucerne Switzerland
Division of Hematology Jewish General Hospital Montreal Quebec Canada
Dubrava University Hospital Zagreb Croatia
Emergency University Clinical Hospital Bucharest Romania
Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy
Galilee Medical Center Nahariya Israel
Hadassah Hebrew University Medical Center Jerusalem Israel
Hematology and Hemotherapy Hospital Universitario Ramón y Cajal Madrid Spain
Hematology Bnai Zion Medical Center Haifa Israel
Hematology Colentina Clinical Hospital Bucharest Romania
Hematology Section 1st Department Of Propaedeutic Internal Medicine Laikon Hospital Athens Greece
Hematology Unit and Biotechnology Research Unit A O of Cosenza Cosenza Italy
Hematology Unit University of Padua Padua Italy
Hospital 12 de Octubre Madrid Spain
Hospital Alvarez Buenos Aires Argentina
Hospital Costa del Sol Marbella Spain
Hospital del Mar Barcelona Spain
Hospital General Universitario Valencia Spain
IIS IP Hospital Universitario de La Princesa Madrid Spain
Institut Jules Bordet Brussels Belgium
Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca Romania
Maxima Medical Center Eindhoven Veldhoven Eindhoven Netherlands
Rabin Medical Center Beilinson Hospital
Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
St John's Cancer Center Lublin Poland
University Hospital and Medical School Hradec Kralove Hradec Kralove Czech Republic
References provided by Crossref.org
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- $a Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group / $c Y. Herishanu, A. Shaulov, R. Fineman, S. Bašić-Kinda, A. Aviv, E. Wasik-Szczepanek, O. Jaksic, M. Zdrenghea, U. Greenbaum, I. Mandac, M. Simkovic, M. Morawska, O. Benjamini, M. Spacek, A. Nemets, O. Bairey, L. Trentin, R. Ruchlemer, L. Laurenti, O. Stanca Ciocan, M. Doubek, L. Shvidel, N. Dali, F. Mirás, A. De Meûter, M. Dimou, FR. Mauro, M. Coscia, H. Bumbea, R. Szász, T. Tadmor, O. Gutwein, M. Gentile, L. Scarfò, A. Tedeschi, P. Sportoletti, E. Gimeno Vázquez, J. Marquet, S. Assouline, M. Papaioannou, A. Braester, L. Levato, M. Gregor, GM. Rigolin, J. Loscertales, A. Medina Perez, MR. Nijziel, VM. Popov, R. Collado, I. Slavutsky, G. Itchaki, S. Ringelstein, N. Goldschmidt, C. Perry, S. Levi, A. Polliack, P. Ghia,
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