%0 Journal Article
%A Herishanu, Yair
%A Shaulov, Adir
%A Fineman, Riva
%A Bašić-Kinda, Sandra
%A Aviv, Ariel
%A Wasik-Szczepanek, Ewa
%A Jaksic, Ozren
%A Zdrenghea, Mihnea
%A Greenbaum, Uri
%A Mandac, Inga
%A Simkovic, Martin
%A Morawska, Marta
%A Benjamini, Ohad
%A Spacek, Martin
%A Nemets, Anatoly
%A Bairey, Osnat
%A Trentin, Livio
%A Ruchlemer, Rosa
%A Laurenti, Luca
%A Stanca Ciocan, Oana
%A Doubek, Michael
%A Shvidel, Lev
%A Dali, Nagib
%A Mirás, Fátima
%A De Meûter, Anne
%A Dimou, Maria
%A Mauro, Francesca R
%A Coscia, Marta
%A Bumbea, Horia
%A Szász, Róbert
%A Tadmor, Tamar
%A Gutwein, Odit
%A Gentile, Massimo
%A Scarfò, Lydia
%A Tedeschi, Alessandra
%A Sportoletti, Paolo
%A Gimeno Vázquez, Eva
%A Marquet, Juan
%A Assouline, Sarit
%A Papaioannou, Maria
%A Braester, Andrei
%A Levato, Luciano
%A Gregor, Michael
%A Rigolin, Gian M
%A Loscertales, Javier
%A Medina Perez, Angeles
%A Nijziel, Marten R
%A Popov, Viola M
%A Collado, Rosa
%A Slavutsky, Irma
%A Itchaki, Gilad
%A Ringelstein, Shimrit
%A Goldschmidt, Neta
%A Perry, Chava
%A Levi, Shai
%A Polliack, Aaron
%A Ghia, Paolo
%T 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.
%D 2020
%U https://hdl.handle.net/10668/26637
%X 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.
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