MURANO Trial Follow-up: MRD and Prognosis With Fixed Duration of Venetoclax/Rituximab in Relapsed or Refractory CLL
As reported in the Journal of Clinical Oncology by Kater et al, high undetectable minimal residual disease (MRD) rates persisted after the end of venetoclax (Venclexta)/rituximab (Rituxan) treatment in the phase III MURANO trial in relapsed or refractory chronic lymphocytic leukemia (CLL), and were associated with improved progression-free survival.
The MURANO trial showed a significant progression-free survival benefit for fixed-duration venetoclax/rituximab vs bendamustine/rituximab in relapsed or refractory CLL.
Study Details
In the trial, patients were randomly assigned to 2 years of venetoclax plus rituximab during the first six cycles, or six cycles of bendamustine/rituximab. All patients are now off venetoclax monotherapy treatment. The current report analyzes MRD kinetics and updated outcomes. Peripheral blood MRD status at cycle 4, 2 to 3 months after end of combination therapy (EOCT), and every 3 to 6 months thereafter was a predefined secondary endpoint of the trial.
Updated Outcomes
Among 194 patients in the venetoclax/rituximab group, 174 (90%) completed the venetoclax/rituximab phase and 130 (67%) completed 2 years of venetoclax. With median follow-up of 36 months, the venetoclax group maintained superior progression-free (hazard ratio [HR] = 0.16, 95% confidence interval [CI] = 0.12–0.23) and overall survival (HR = 0.50, 95% CI = 0.30–0.85) vs bendamustine/rituximab.
MRD and Progression-Free Survival
Undetectable peripheral blood MRD (<10-4) was found at EOCT in 62% of the venetoclax group vs 13% of the control group. At end of venetoclax monotherapy therapy at month 24, undetectable MRD was maintained in 83 (64%) of 130 patients treated with venetoclax.
Among all patients, undetectable MRD status at EOCT predicted longer progression-free survival; for example, vs low-level MRD (10-4 to < 10-2), hazard ratios were 0.48 (95% CI = 0.24–0.98) in the venetoclax group and 0.44 (95% CI =0.22–0.89) in the control group. Low level MRD was also associated with improved progression-free survival vs high level MRD (≥10-2).
At the current follow-up at a median of 9.9 months off venetoclax, progressive disease had developed in only 2 (2.4%) of 83 patients in the venetoclax group who had undetectable MRD at end of therapy; overall, progressive disease was observed in 16 (12%) of 130 patients, with the remaining 14 cases occurring in 11 patients with high-level MRD and 3 patients with low-level MRD at end of treatment. At this follow up, undetectable MRD persisted in 58 (70%) of 83 patients with undetectable MRD at end of therapy.
The investigators concluded, “With all patients having finished treatment, continued benefit was observed for venetoclax/rituximab compared with bendamustine/rituximab. [Undetectable] MRD rates were durable and predicted longer [progression-free survival], which establishes the impact of [peripheral blood] MRD on the benefit of fixed-duration, venetoclax-containing treatment. Low conversion to detectable MRD and sustained [progression-free survival] after completion of 2 years of venetoclax/rituximab demonstrate the feasibility of this regimen.”
Arnon P. Kater, MD, PhD, of the Department of Hematology and Lymphoma and Myeloma Center, Cancer Center Amsterdam, Amsterdam UMC, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Genentech and AbbVie. The study authors’ full disclosures can be found at jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
