KEY TAKEAWAYS
- The study aimed to investigate the superior efficacy of personalized ibrutinib-venetoclax therapy, guided by MRD vs FCR in CLL pts.
- The primary endpoint was to determine PFS.
- Researchers concluded that MRD-directed ibrutinib-venetoclax demonstrated superior PFS and favorable OS compared to FCR in CLL.
The combination of ibrutinib and venetoclax has demonstrated improved outcomes in chronic lymphocytic leukemia (CLL) compared to chemoimmunotherapy. Talha Munir and his team aimed to investigate whether ibrutinib-venetoclax, with personalized treatment duration based on measurable residual disease (MRD), is more effective than fludarabine-cyclophosphamide-rituximab (FCR) is unclear.
Researchers performed an inclusive analysis within a phase 3, multicenter, randomized, controlled, open-label platform trial involving untreated CLL patients. A comparison was made between ibrutinib-venetoclax and ibrutinib monotherapy versus FCR. In the ibrutinib-venetoclax group, venetoclax supplementation followed 2 months of ibrutinib for up to 6 years, with therapy duration determined by MRD in peripheral blood and bone marrow, set at double the time required for achieving undetectable MRD. The primary endpoint assessed was progression-free survival in the ibrutinib-venetoclax group compared with FCR. Key secondary endpoints encompassed overall survival, response rates, MRD status, and safety outcomes.
About 523 patients were randomly assigned to either the ibrutinib-venetoclax group or the FCR group. After a median follow-up of 43.7 months, disease progression or death occurred in 12 patients in the ibrutinib-venetoclax group and 75 patients in the FCR group (HR, 0.13; 95% CI, 0.07 to 0.24; P<0.001). In the ibrutinib-venetoclax group, 9 deaths were reported compared to 25 pts in the FCR group (HR, 0.31; 95% CI, 0.15 to 0.67).
At the 3-year mark, 58.0% of patients in the ibrutinib-venetoclax group discontinued therapy due to undetectable MRD. Following 5 years of ibrutinib-venetoclax treatment, 65.9% had undetectable MRD in the bone marrow, and 92.7% had undetectable MRD in the peripheral blood.
The risk of infection was comparable between the ibrutinib-venetoclax and FCR groups. However, the ibrutinib-venetoclax group exhibited a higher percentage of patients with cardiac serious adverse events compared to the FCR group (10.7% vs. 0.4%).
The study concluded that MRD-directed ibrutinib-venetoclax not only improved progression-free survival compared to FCR but also demonstrated favorable overall survival outcomes.
The study is sponsored by Cancer Research UK
Source: https://pubmed.ncbi.nlm.nih.gov/38078508/
Munir T, Cairns DA, Bloor A, et al (2024). National Cancer Research Institute Chronic Lymphocytic Leukemia Subgroup. “Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease.” N Engl J Med. 2024 Jan 25;390(4):326-337. doi: 10.1056/NEJMoa2310063. Epub 2023 Dec 10. PMID: 38078508.
