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

• Authors: HERISHANU Y.; SHAULOV A.; FINEMAN R.; BASIC-KINDA S.; AVIV A.; WASIK-SZCZEPANEK E.; JAKSIC O.; ZDRENGHEA M.; GREENBAUM U.; MANDAC I.; SIMKOVIC M.; MORAWSKA M.; BENJAMINI O.; SPACEK M.; NEMETS A.; BAIREY O.; TRENTIN L.; RUCHLEMER R.; LAURENTI L.; CIOCAN O. S.; DOUBEK Michael; SHVIDEL L.; DALI N.; MIRAS F.; DE METEUR A.; DIMOU M.; MAURO F. R.; COSCIA M.; BUMBEA H.; SZASZ R.; TADMOR T.; GUTWEIN O.; GENTILE M.; SCARF L.; TEDESCHI A.; SPORTOLETTI P.; GIMENO VAZQUEZ E.; MARQUET J.; ASSOULINE S.; PAPAIOANNOU M.; BRAESTER A.; LEVATO L.; GREGOR M.; RIGOLIN G. M.; LOSCERTALES J.; PEREZ A. M.; NIJZIEL M. R.; POPOV V. M.; COLLADO R.; SLAVUTSKY I.; ITCHAKI G.; RINGELSTEIN S.; GOLDSCHMIDT N.; PERRY C.; LEVI S.; POLLIACK A.; GHIA P.
• Year of publication: 2020
• Type: Article in Periodical
• Magazine / Source: American Journal of Hematology
• MU Faculty or unit: Faculty of Medicine
• Web: https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25766
• Doi: http://dx.doi.org/10.1002/ajh.25766
• Keywords: RITUXIMAB REGIMEN; THERAPY; CYCLOPHOSPHAMIDE; FLUDARABINE; IBRUTINIB
• Description: 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.