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

RIVA FINEMAN; EWA WASIK-SZCZEPANEK; URI GREENBAUM; MARTA MORAWSKA; ANATOLY NEMETS; ROSA RUCHLEMER; MICHAEL DOUBEK; FÁTIMA MIRÁS; FRANCESCA R. MAURO; RÓBERT SZÁSZ; MASSIMO GENTILE; PAOLO SPORTOLETTI; SARIT ASSOULINE; LUCIANO LEVATO; JAVIER LOSCERTALES; VIOLA M. POPOV; GILAD ITCHAKI; CHAVA PERRY; PAOLO GHIA; YAIR HERISHANU; SANDRA BASIK-KINDA; OZREN JAKSIC; INGA MANDAC; OHAD BENJAMINI; OSNAT BAIREY; LUCA LAURENTI; LEV SHVIDEL; ANNE DE MEÛTER; MARTA COSCIA; TAMAR TADMOR; LYDIA SCARFÒ; EVA GIMENO VÁZQUEZ; ADIR SHAULOV; MARIA PAPAIOANNOU; ARIEL AVIV; MICHAEL GREGOR; MIHNEA ZDRENGHEA; ANGELES MEDINA PEREZ; MARTIN SIMKOVIC; ROSA COLLADO; MARTIN SPACEK; SHIMRIT RINGELSTEIN; LIVIO TRENTIN; SHAI LEVI; OANA STANCA CIOCAN; NAGIB DALI; MARIA DIMOU; HORIA BUMBEA; ODIT GUTWEIN; ALESSANDRA TEDESCHI; JUAN MARQUET; ANDREI BRAESTER; GIAN M. RIGOLIN; MARTEN R. NIJZIEL; IRMA SLAVUTSKY; NETA GOLDSCHMIDT; AARON POLLIACK

AMERICAN JOURNAL OF HEMATOLOGY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2020 vol. 11

0361-8609

In recent years, considerable progress has been made in frontline therapy of elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given together with either ibrutinib or venetoclax improved PFS, although not OS, compared to O-Clb. In this retrospective multinational and 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 CRIS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate (ORR) was 86.5% (complete and partial responses in 41.6% and 45.8% of patients, respectively). The median observation time was 14.1 months and the 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>5cm, obinutuzumab monotherapy, reduced cumulative dose of obinutuzumab and clinical response of less than CR, 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 observed in patients with del(11q22.3) and/or unmutated IGHV and those treated with G-monotherapy. Thus, O-Clb can be still considered as legitimate frontline treatment for unfit CLL patients with low-risk disease.