Venetoclax Plus Rituximab in Relapsed CLL: Genomic Complexity and Outcomes
Posted: Tuesday, November 24, 2020
The combination of venetoclax plus rituximab improved outcomes compared with bendamustine plus rituximab for patients with relapsed chronic lymphocytic leukemia (CLL), according to the 4-year results from the phase III MURANO trial, published in the Journal of Clinical Oncology. In addition, John F. Seymour, MD, PhD, of the Royal Melbourne Hospital, Melbourne, Australia, and colleagues found that genetic mutations and genomic complexity seemed to affect minimal residual disease (MRD) rates and progression-free survival.
“This analysis of MURANO study data establishes novel associations between candidate biomarkers and clinical outcomes with venetoclax plus rituximab therapy,” the authors commented.
In this study, 389 patients with relapsed CLL were enrolled. Of the total, 194 randomly received venetoclax plus rituximab, and 195 randomly received bendamustine plus rituximab. In the first group, the patients received six 28-day cycles of venetoclax plus rituximab and single-agent venetoclax (400 mg) once daily for 2 years. The second group was treated with six 28-day cycles of standard bendamustine plus rituximab. Progression-free survival, overall survival, peripheral blood MRD status, genomic complexity, and gene mutations were evaluated. Genomic complexity was assessed at the Laboratory of Genome Diagnostics of the Amsterdam University Medical Centers of the University of Amsterdam.
The 4-year progression-free survival and overall survival rates were improved with venetoclax plus rituximab, and undetectable MRD at the end of combination therapy was linked with a better progression-free survival. Progression-free survival rates with venetoclax plus rituximab and bendamustine plus rituximab were 57.3% and 4.6%, respectively. Overall survival rates were 85.3% and 66.8%, respectively. In the venetoclax-plus-rituximab group, patients treated with ibrutinib after disease progression had a response rate of 100%. The undetectable MRD rate was lower in patients with genomic complexity compared with those without genomic complexity among patients receiving venetoclax plus rituximab. A higher genomic complexity was linked to shorter progression-free survival.
Disclosure: The study authors’ disclosure information can be found at ascopubs.org.
