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

Abstract

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 >5cm, 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) This article is protected by copyright. All rights reserved. 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.

Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study

“…18 Likewise, an 80.3% ORR and estimated 2-year OS of 88% was recorded by the Israeli end ERIC group in elderly patients who received chlorambucil and obinutuzumab, without unexpected adverse events. 32 Taken together, these data show that the efficacy and safety of different CIT regimens in routine clinical practice are consistent with those reported in clinical trials.…”

“…It is worth noting that chlorambucil and rituximab produced an 87% ORR with an OS rate at 48 and 60 months of 86.1% (95% CI: 79.4‐93.5) and 81.2% (95% CI: 72.4‐91.2), respectively, in elderly patients treated outside clinical trials 18 . Likewise, an 80.3% ORR and estimated 2‐year OS of 88% was recorded by the Israeli end ERIC group in elderly patients who received chlorambucil and obinutuzumab, without unexpected adverse events 32 . Taken together, these data show that the efficacy and safety of different CIT regimens in routine clinical practice are consistent with those reported in clinical trials.…”

Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

“…This treatment showed a complete remission rate of 32%, but also the occurrence of toxicities as tumor lysis syndrome [ 30 ]. The efficacy of G-Chl regimen in CLL patients with comorbidities has been assessed in CLL11 trial [ 5 , 31 ], which led to its approval by FDA and EMA as a first-line treatment in patients with comorbidities (CIRS > 6 and/or CrCl < 70 mL/min) and in real-life studies [ 32 , 33 ]. The CLL11 study also showed that Chl-R achieves longer PFS (median 16 versus 11 months) and overall survival (OS) than chlorambucil monotherapy.…”

Healthcare Utilization and Comorbidity in Chronic Lymphocytic Leukemia

“…Real-world data from our group and others show that patients receiving Clb-based regimens have a median age of 76–80 years, and it remains to accurately determine these patients’ tolerance of targeted treatment and need for supportive care. 22 , 49 …”