As reported in the Journal of Clinical Oncology by Arnon P. Kater, MD, PhD, of Amsterdam University Medical Centers, and colleagues,1 the 4-year progression-free and overall survival rates were significantly higher with venetoclax plus rituximab vs bendamustine plus rituximab in the phase III MURANO trial in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). The investigators also provided findings on the effect of genomic complexity and mutations on treatment outcomes.
In the trial, 389 patients were randomly assigned to receive 2 years of daily venetoclax plus six cycles of rituximab (n = 194) or six cycles of bendamustine plus rituximab. In previous analyses, venetoclax/rituximab was associated with significantly prolonged progression-free survival vs bendamustine/rituximab.
Arnon P. Kater, MD, PhD
At 4 years, progression-free survival (57.3% vs 4.6%, hazard ratio [HR] = 0.19, 95% confidence interval [CI] = 0.14–0.25) and overall survival (85.3% vs 66.8%, HR = 0.41, 95% CI = 0.26–0.65) rates were significantly improved with venetoclax/rituximab vs bendamustine/rituximab. The overall survival benefit of venetoclax/rituximab was observed, despite the receipt of novel
targeted agents after disease progression in 81 patients in the bendamustine/rituximab group vs 28 patients in the venetoclax/rituximab group. Responses were achieved in each of 10 evaluable patients in the venetoclax/rituximab group who received ibrutinib as first therapy after disease progression and in 6 of 11 who received a venetoclax-based regimen.
Patients with undetectable minimal residual disease (MRD) at the end of combination therapy had the most favorable outcomes in both groups. In the venetoclax/rituximab group, hazard ratios for progression-free survival were 0.50 (P = .02) for undetectable MRD vs low MRD positivity, 0.15 (P < .0001) for undetectable MRD vs high MRD positivity, and 0.25 (P = .002) for low vs high MRD positivity.
In the venetoclax/rituximab group, progression-free survival rates at 18 months after the end of treatment were 90.3% in patients with undetectable MRD, 64.4% in those with low MRD positivity, and 8.3% in those with high MRD positivity.
Among patients in the venetoclax/rituximab group with genomic complexity data, the undetectable MRD rate at the end of treatment was lower in patients with genomic complexity than in those without (P = .042). Undetectable MRD rates were 64.4% among 73 patients with noncomplex status, 57.7% among 27 with low genomic complexity, and 50% among 10 with high genomic complexity. Patients with noncomplex status had significantly better progression-free survival vs those with high genomic complexity (HR = 2.9, P = .0057) and vs those with low genomic complexity (HR = 2.0, P = .025).
Lower undetectable MRD rates were observed at the end of combination treatment in patients receiving venetoclax/rituximab with BRAF or BIRC3 mutations compared with patients who had wild-type disease. Lower undetectable MRD rates were observed at the end of treatment in patients receiving venetoclax/rituximab with TP53, NOTCH1, XPO1, and BRAF mutations.
The investigators concluded: “Efficacy benefits with fixed-duration venetoclax/rituximab are sustained and particularly durable in patients who achieve undetectable MRD.
Disclosure: The study was supported by Genentech and AbbVie. For full disclosures of the study authors, visit ascopubs.org.
1. Kater AP, Wu JQ, Kipps T, et al: Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia. J Clin Oncol. September 28, 2020 (early release online).