A combination of Venclexta (venetoclax) plus Rituxan (rituximab) was better than standard of care at extending the duration of undetectable residual disease in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to a Phase 3 trial.
The findings were presented at the 23rd European Hematology Association (EHA) Annual Congress June 14-17 in Stockholm, Sweden.
The presentation was titled, “High, Durable Minimal Residual Disease (MRD) Negativity with Venetoclax + Rituximab in Relapsed/Refractory CLL: MRD Kinetics and Responses in Cytogenetic Risk Groups in PTS from Phase 3 MURANO Study.”
In blood cancers, minimal residual disease (MRD) refers to a small number of malignant cells that remain in the body after treatment is complete. These cells can sometimes be present at levels undetectable by traditional diagnostic methods, so they can persist and proliferate, causing a relapse of the disease.
Having undetectable MRD (uMRD) means that fewer than one in every 10,000 white blood cells in the blood or bone marrow is a cancer cell. This is thought to be a predictor of better responses to treatment and survival outcomes.
CLL is a form of leukemia, or blood cancer, that worsens slowly. Too many immature lymphocytes (a type of white blood cell) are found in the blood and bone marrow of patients, causing the disease.
On June 8, the U.S. Food and Drug Administration approved the Venclexta-Rituxan combination for the treatment of patients with CLL or small lymphocytic lymphoma (SLL).
The Phase 3 MURANO trial (NCT02005471) was designed to determine if Venclexta plus Rituxan was better at extending the time a patient lived without disease worsening than Rituxan plus bendamustine, the standard chemotherapy regimen used for CLL patients. It also assessed the proportion of patients achieving a response to treatment.
Results showed that patients receiving Venclexta (marketed by AbbVie and Genentech) had an 83% lower risk for disease worsening or death, and that more patients on Venclexta achieved undetectable MRD.
To determine if a patient’s MRD status correlates with their outcomes, researchers now followed the patients’ MRD status at various timepoints.
Among the 194 patients receiving Venclexta plus Rituxan (co-marketed by Genentech and Biogen), 121 patients (62%) achieved undetectable MRD at the end of the combination treatment. After a median followup of 13.8 months, 100 of the 121 patients remained progression-free and with undetectable MRD.
At an undisclosed timepoint, 84% of patients receiving Venclexta had undetectable MRD. This was the best MRD negativity rate achieved with this combination. For those receiving bendamustine plus Rituxan, the best rate was 23%.
Researchers also found that MRD negativity in the blood correlates with the outcomes of relapsed or refractory patients receiving Venclexta.
“In this analysis of 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,” Peter Hillmen, PhD, a professor of experimental hematology at Leeds Teaching Hospital in the U.K., and lead investigator of the MURANO study, said in a press release.
“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,” he added.
Neil Gallagher, an MD and PhD, and head of global oncology development at AbbVie, said the Venclexta results presented at the EHA Annual Congress “adds to the growing body of evidence that supports a correlation between undetectable minimal residual disease (MRD) and improved clinical outcomes for patients with chronic lymphocytic leukemia.”