ASH 2022: High Rates of Progression-Free Survival and MRD Undetectability in Patients with Chronic Lymphocytic Leukemia Receiving Ibrutinib Plus Venetoclax

Investigators reported updated results from a phase II trial exploring the use of ibrutinib-venetoclax combination therapy in patients with high-risk chronic lymphocytic leukemia (CLL). Results of the study involving 80 patients were previously published in 2019 and 2021. Here, investigators provided a four-year update on these patients plus an additional 40 others included as part of a study expansion.

The study included patients with previously untreated CLL with at least one high-risk feature of disease: del(17p), mutated TP53, del(11q), unmutated IGHV, or age 65 years or greater. Combination therapy was given for twenty-four 28-day cycles, with up to 12 additional cycles given for patients who remained bone marrow (BM) minimal residual disease (MRD)-positive at the end of 24 cycles.

Fifty-two percent of patients achieved MRD undetectability by cycle 12; after 24 cycles of combination therapy, 64% achieved BM undetectable-MRD. Of the 24 patients who remained BM MRD-positive after 24 cycles, 18 with low MRD positivity resumed combination therapy. Of these patients, 61% achieved undetectable MRD during a third year of treatment. The four-year rates of progression-free and overall survival were 94.5% and 96.6%, respectively.

The only high-risk disease feature found to be associated with MRD detectability was the presence of a TP53 mutation, which was associated with a lower rate of BM undetectable-MRD at six months. However, this association was lost at 12 months. None of the high-risk features included were associated with progression-free survival.