Patients with previously untreated chronic lymphocytic leukemia (CLL) who were eligible for treatment were enrolled in this study of ibrutinib combined with venetoclax. All patients had at least 1 of the following high-risk features: del(17p), mutated TP53, del(11q), unmutated IGHV, or age of 65 years or older. In this study, patients received ibrutinib alone (monotherapy) for 3 cycles followed by the addition of venetoclax. Combined therapy was then administered for 24 cycles.
In this study, patients found to have undetectable minimal residual disease (MRD), known as “MRD negative,” stopped both drugs. Those with evidence of MRD (“MRD positive”) continued ibrutinib. Progression-free survival (PFS) is defined as the time from the start of the study drug to disease progression; transformation to more aggressive disease (Richter’s transformation); or death. Overall survival is defined as the time from initial use of the study drugs to death.
A total of 80 patients enrolled in this study. Their median age was 65 years. About one-third (30%) of these patients were 70 years of age or older. Overall, 92% of patients had unmutated IGHV, TP53 aberration, or del(11q). Five of 80 patients went off study during ibrutinib monotherapy, leaving 75 patients who received ibrutinib plus venetoclax.
After 3 cycles of ibrutinib monotherapy, none of the 75 patients were MRD negative. After the addition of venetoclax, increasing numbers of patients became undetectable MRD negative. After 3 cycles of ibrutinib plus venetoclax, 16% of patients had undetectable MRD. After 6 cycles, this increased to 42%. After 12 cycles, 65% had undetectable MRD. After 24 cycles of ibrutinib plus venetoclax, this increased to 79%.
Median patient follow-up time is now 23 months. No patient has had progression of their CLL. Richter’s transformation developed in 2 patients, a 63-year-old and a 67-year-old with CLL; both had high-risk genomics. Three patients died.
Researchers concluded that the combination of ibrutinib plus venetoclax is an effective chemotherapy-free oral regimen for patients with high-risk previously untreated CLL. Ongoing comparative studies will help to define the role of this combination regimen in patients with CLL.
Abstract 34. ASH 2019.