Measurable Residual Disease as a Treatment Guide for Patients with Chronic Lymphocytic Leukemia

In new research, Talha Munir, PhD, Leeds Cancer Centre, Leeds, United Kingdom, and colleagues studied the outcomes of patients with chronic lymphocytic leukemia (CLL) who took a combination therapy of ibrutinib and venetoclax that was guided by their measurable residual disease (MRD). In this study, fludarabine-cyclophosphamide-rituximab (FCR) was used as a control group to compare their results.

Dr Munir compared ibrutinib-venetoclax with ibrutinib monotherapy with FCR. After two months of ibrutinib treatment, patients in the ibrutinib-venetoclax group received venetoclax for at most six years. The researchers came up with this time period for treatment using MRD from their blood and bone marrow assessments. Their main goal in this study was for a higher progression-free survival rate in the ibrutinib-venetoclax group than in the FCR group. They also sought to improve the overall survival rate, response to treatment, MRD, and safety of patients with CLL.

In total, 523 patients participated in the study. All patients were randomly assigned to either the ibrutinib-venetoclax group or the FCR group. After 43.7 months, the researchers found that CLL had progressed in 12 patients in the ibrutinib-venetoclax group. In the FCR group, 75 patients with CLL experienced disease progression. In the ibrutinib-venetoclax group, nine patients died, while 25 patients died in the FCR group. After three years of treatment, about half (58.0%) of patients in the ibrutinib group discontinued treatment because of undetectable MRD. This percentage continued to rise after five years, with 65.9% of patients showing undetectable MRD in their bone marrow and 92.7% showing undetectable MRD in their peripheral blood. Both groups in this study had similar rates of infection; however, Dr Munir did find that the risk of a serious cardiac adverse event was higher in the ibrutinib-venetoclax group (10.7% vs 0.4%).

“MRD-directed ibrutinib–venetoclax improved progression-free survival as compared with FCR, and results for overall survival also favored ibrutinib–venetoclax,” the authors wrote.

Overall, the study found an improvement in progression-free survival, overall survival, safety, and patient response in the ibrutinib-venetoclax group in comparison to the FCR group. The researchers concluded that more research needs to be done with other types of cancers to determine the full impact of MRD on guiding treatment.

Source: Munir T, Cairns DA, Bloor A, et al. Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. N Engl J Med. 2024; 390:326-337. doi:10.1056/nejmoa2310063