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Fixed Duration Venetoclax Plus Rituximab Provides Long-Term Benefit vs Bendamustine Plus Rituximab in CLL
Benefits associated with venetoclax plus rituximab treatment over bendamustine plus rituximab were maintained at 3 years following cessation in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to a 5-year update of the phase 3 MURANO trial published in Blood.
“The phase 3 trial investigated the efficacy and safety of fixed-duration therapy with venetoclax plus rituximab for 6 months followed by single-agent [venetoclax] for up to a total duration of 2 years, compared with 6 months of bendamustine plus rituximab, in patients with [relapsed/refractory] CLL,” John F. Seymour, MD, Peter MacCallum Cancer Centre, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia, and colleagues wrote.
This trial reported superior progression-free survival (PFS) and overall survival (OS) with venetoclax-rituximab vs bendamustine-rituximab in relapsed/refractory (R/R) CLL. Patients were randomized to 2 years of venetoclax plus rituximab (n = 194; rituximab for the first 6 months) or 6 months of bendamustine-rituximab (n = 195).
Although undetectable minimal residual disease (uMRD) was achieved more often with venetoclax-rituximab, the long-term implications of uMRD with this fixed-duration, chemotherapy-free regimen have not been explored. In this study, they reported MRD kinetics and updated outcomes with 5 years’ follow-up.
At 5 years of follow-up, the median PFS with venetoclax-rituximab vs bendamustine-rituximab was 53.6 months (95% confidence interval [CI], 48.4 to 57) vs 17 months (95% CI, 15.5 to 21.7) with bendamustine plus rituximab (P <.0001). The 5-year OS was 82.1% (95% CI, 76.4 to 87.8) vs 62.2% (95% CI, 54.8 to 69.6), respectively (P <.0001).
Venetoclax-rituximab was found to be superior to bendamustine-rituximab, regardless of cytogenetic category. Venetoclax-rituximab -treated patients with uMRD at end of treatment (EOT; n = 83) had superior OS vs those with high-MRD positivity (n = 12): 3-year post-EOT survival rates were 95.3% vs 72.9%, respectively (P = .039).
In those with uMRD at EOT, median time to MRD conversion was 19.4 months. Of 47 patients with documented MRD conversion, 19 developed progressive disease; median time from conversion to progressive disease was 25.2 months. A population-based logistic growth model indicated slower MRD median doubling time post-EOT with venetoclax-rituximab (93 days) vs bendamustine-rituximab (53 days; P = 1.2 × 10−7). No new safety signals were identified. Sustained survival, uMRD benefits, and durable responses support 2-year fixed-duration venetoclax plus rituximab treatment in relapsed/refractory CLL.
“In this update of MURANO, sustained survival benefits are shown with [venetoclax-rituximab] over bendamustine-rituximab, up to 3 years’ post-completion of fixed-duration treatment and all patients off-therapy, regardless of the presence of high-risk cytogenetic biomarkers,” they concluded. “These data further support the use of fixed-duration [venetoclax-rituximab] in patients with R/R CLL.”
Source:
Seymour JF, Kipps TJ, Eichhorst BF, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8):839-850. doi:10.1182/blood.2021015014
