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

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.Fil: Herishanu, Yair. Universitat Tel Aviv; IsraelFil: Shaulov, Adir. Hadassah Hebrew University Medical Center; IsraelFil: Fineman, Riva. Rambam Health Care Campus; IsraelFil: Basik Kinda, Sandra. University Hospital Centre Zagreb; CroaciaFil: Aviv, Ariel. Technion - Israel Institute of Technology; IsraelFil: Wasik Szczepanek, Ewa. Medical University of Lublin; PoloniaFil: Jaksic, Ozren. Dubrava University Hospital, Zagreb; CroaciaFil: Zdrenghea, Mihnea. Luliu Hatieganu University Of Medicine And Pharmacy; RumaniaFil: Greenbaum, Uri. oroka University Medical Center; Israel. Ben Gurion University; IsraelFil: Mandac, Inga. Clinical Hospital Merkur; CroaciaFil: Simkovic, Martin. University Hospital And Medical School Hradec Kralove; República ChecaFil: Morawska, Marta. St. John's Cancer Center; PoloniaFil: Benjamini, Ohad. Chaim Sheba Medical Center, Ramat Gan; IsraelFil: Spacek, Martin. Charles University And General Hospital In Prague; República ChecaFil: Nemets, Anatoly. Barzilai University Medical Center; IsraelFil: Bairey, Osnat. Universitat Tel Aviv; IsraelFil: Trentin, Livio. Università di Padova; ItaliaFil: Ruchlemer, Rosa. Shaare Zedek Medical Center; IsraelFil: Laurenti, Luca. Fondazione Policlinico Universitario Agostino Gemelli; ItaliaFil: Ciocan, Oana Stanca. Coltea Clinical Hospital; RumaniaFil: Doubek, Michael. University Hospital Brno; República Checa. Masaryk University; República ChecaFil: Shvidel, Lev. The Hebrew University of Jerusalem; IsraelFil: Dali, Nagib. Ziv Medical Center; IsraelFil: Mirás, Fátima. Hospital 12 de Octubre; EspañaFil: De Meûter, Anne. Institut Jules Bordet; BélgicaFil: Dimou, María. Laikon Hospital; GreciaFil: Mauro, Francesca R.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Coscia, Marta. Università di Torino; ItaliaFil: Bumbea, Horia. Emergency University Clinical Hospital; RumaniaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin