Fixed-duration venetoclax combination equivalent to continuous ibrutinib in head-to-head comparison in CLL

In the first head-to-head trial comparing two treatment strategies, a fixed-duration regimen featuring the BCL2 inhibitor venetoclax was effective in patients with chronic lymphocytic leukemia (CLL) provides the same clinical benefits as open-label treatment with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib/ibrutinib (Ibrutinib). Results for CLL17 (NCT04608318) were announced earlier.

Results show that after 3 years, patients who received a fixed-duration andibrutinib regimen plus venetoclaxandobinutuzumab monoclonal antibody therapy had progression-free survival (PFS) similar to patients who received a continuousibrutinib regimen.

CLL is a common form of leukemia in the United States and Europe, and is most likely to affect patients over the age of 65. Of course, this has many implications for treatment tolerability, side effects, and drug interactions. These are clinically important considerations. Fixed-duration treatment regimens provide these patients with relief from treatment.

The aim here is to combine and produce deep remission, allowing the patient to discontinue treatment while maintaining remission. Ideally, patients will be given" years of treatment-free intervals where they can control their CLL but not require medical intervention.

According to the study protocol, patients in the intravenous toin sodiumobinutuzumab group received six cycles (28 days each) of both treatments, followed by six additional cycles of venetoclax monotherapy. In the ibrutinib group, 3 cycles of ibrutinib were first introduced, followed by 12 cycles of the combination. Patients in the ibrutinib monotherapy group continued treatment until disease progression.

The three-year progression-free survival rates in each group were within the 6% difference that defined non-inferiority in the study: 81.1% in the venetoclax-obinutuzumab group; ibrutinib 81.0% in the ibrutinib group; 79.4% in the ibrutinib group.

Compared with the ibrutinib group, the hazard ratio (HR) of the venetoclax-obinutuzumab group was 0.87, and the type I error-adjusted CI (98.3%) was 0.54-1.41; compared with the ibrutinib group, the dimension The HR in the Neclatra-ibrutinib group was 0.84, and the type I error-adjusted CI (98.0%) was 0.53-1.32). The upper limit of each adjusted CI was below the predefined noninferiority margin, providing early evidence of noninferiority.

Secondary endpoints reported by the investigators included the overall response rate in the final stage, which was 84.2% in the venetoclax-obinutuzumab group and 88.5% in the ibrutinib group. >Veneclat-The ibrutinib group was86.0%; the complete response rates were 51.5%, 46.2% and 8.3% respectively. In patients with unmutated IGHV, 3-year PFS was 75.8% in the venetuzumab group (87.6% in the mutated IGHV group), 79.7% (83.5%) in the ibrutinib group, and 78.9% (80.0%) in the ibrutinib group.

The most common adverse events (AE) are as follows: infections and infestations, gastrointestinal disorders, blood and lymphatic system disorders; Cardiac disease is a known adverse event of ibrutinib. Notably, second-generation BTK inhibitors have reported lower cardiotoxicity than ibrutinib.

Reference materials:https://www.ajmc.com/view/in-cll-fixed-duration--combos-are-equal-to-continuous-ibrutinib-in-head-to-head-comparison