EHA 2018: Undetectable MRD Rates With Venetoclax Plus Rituximab in Relapsed or Refractory CLL
Investigational data from a new analysis of undetectable minimal residual disease (MRD) rates from the phase III MURANO trial of venetoclax (Venclexta, a first-in-class oral B-cell lymphoma 2 [BCL2] inhibitor) in combination with rituximab (Rituxan) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) was presented by Hillmen et al at the 23rd Annual Congress of the European Hematology Association (EHA) (Abstract S805).
Of the 121 patients who achieved undetectable MRD (meaning < 1 CLL cell in 10,000 white blood cells were detectable using a standardized test) at the end of combination therapy, 83% (n = 100) maintained undetectable MRD and were progression-free for a median of 13.8 months (range = 5.6–23.0 months) thereafter.
“In this analysis of [undetectable MRD] data in patients with chronic lymphocytic leukemia given venetoclax in combination with rituximab, high and durable undetectable MRD rates were achieved in peripheral blood at the end of combination treatment assessment regardless of the risk features,” said Peter Hillmen, PhD, Professor of Experimental Hematology at Leeds Teaching Hospital and lead investigator of the MURANO study. “These undetectable MRD results, along with data regarding the nearly 14-month progression-free findings in patients who maintained undetectable MRD, are an encouraging finding from the MURANO study.”
Study Design and Results
The international, multicenter, open-label, randomized phase III MURANO study included a total of 389 patients with relapsed or refractory CLL who had received at least one prior therapy. The study was designed to evaluate the efficacy (primary endpoint of investigator-assessed progression-free survival) and safety of venetoclax in combination with rituximab (194 patients; median age = 64.5 years) for up to 2 years compared with bendamustine in combination with rituximab (195 patients; median age = 66.0 years) for 6 months.
For the analysis, peripheral blood samples were serially collected (at end of combination therapy, month 9; and every 12 weeks thereafter for up to 3 years), whereas bone marrow samples were collected at the end of combination therapy or at best response. MRD was analyzed centrally by allele-specific oligonucleotide polymerase chain reaction assessment and/or flow cytometry.
A high peripheral blood/bone marrow MRD concordance was seen with venetoclax plus rituximab in patients with paired samples (84%). Achievement of undetectable MRD was independent of risk factors, including del(17p), IgVH mutation, and TP53 mutations.
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