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.
|Number of pages||8|
|Journal||American Journal of Hematology|
|State||Published - 1 Jun 2020|
Bibliographical noteFunding Information:
YH‐ has reported honoraria from AbbVie, Janssen, Astra‐Zeneca and Roche. MD has reported honoraria and research grants from Roche, AbbVie, AOP Orphan Pharmaceuticals, Gilead, Novartis and Jannsen. JL‐AdBoards/honoraria: Janssen, Abbvie. AdBoard: AstraZeneca. Honoraria: Roche, Gilead. RGM‐ has reported grants: Gilead, Janssen. Research support: Gilead and honoraria: Gilead, Abbvie. PG has reported Honoraria/advisory board: AbbVie, Acerta/AstraZeneca, Adaptive, ArQule, BeiGene, CelGene/Juno, Dynamo, Gilead, Janssen, Sunesis. Research Funding: AbbVie, Gilead, Janssen, Novartis, Sunesis.
© 2020 Wiley Periodicals, Inc.