STOCKHOLM – A chemotherapy-free regimen of ibrutinib plus venetoclax was generally safe and showed promising early efficacy in patients with relapsed or refractory chronic lymphocytic leukemia, investigators reported.
A planned interim analysis performed after the first 15 patients who had received two cycles of ibrutinib plus one of ibrutinib and venetoclax showed no treatment-related deaths or treatment interruptions, and all patients had clinical responses, including 8 with complete clinical remission (CR), reported, from Rigshospitalet in Copenhagen, and his colleagues.
The goal of the ongoingstudy is to evaluate whether minimal residual disease (MRD)–guided therapy with the Bruton tyrosine kinase inhibitor ibrutinib and the BCL2 inhibitor venetoclax could lead to MRD negativity and allow select patients to stop treatment, Dr. Niemann said in an interview at the annual congress of the European Hematology Association.
“It’s a 100% clinical response rate and 53% CR. Obviously these are clinical responses, so we don’t have the CT scans, we don’t have the bone marrow biopsies, but we’re very happy to see even in the relapsed/refractory setting such good response rates,” he said.
The investigators are enrolling patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic leukemia requiring treatment and starting all patients on ibrutinib 420 mg daily for the first 2 cycles, with venetoclax added in a 5-week ramp-up from 20 mg beginning with cycle 3 to a final dose of 400 mg daily for 15 total treatment cycles.
At the end of the induction phase, patients who are determined to be MRD-negative by flow cytometry at cycles 12 and 15, and by bone marrow at cycle 15, are randomized on a 1:2 basis to ibrutinib maintenance until disease progression or intolerable toxicity, or to observation until progression or loss of MRD negativity, at which time they start maintenance with ibrutinib until progression or toxicity, plus 12 months of venetoclax.
All 15 patients who were followed for 3 months had clinical responses, including 8 CRs (53%), 6 partial remissions (40%), and 1 partial remission with lymphocytosis (7%).
Three patients had ibrutinib dose reductions and two had venetoclax dose reductions, but no patients stopped treatment. Three patients had grade 2 adverse events (AEs), three had grade 3 AEs, and two had grade 4 AEs. There were no grade 5 AEs.
Two patients had serious AEs during the first two cycles with ibrutinib alone, one of which was a case of febrile neutropenia and one which was an adenocarcinoma of the lung. There were no serious AEs reported during venetoclax ramp-up. To date, there have been no cases of tumor lysis syndrome, atrial fibrillation, or bleeding events reported.
The results suggest that treatment with ibrutinib and venetoclax ramp-up is manageable in this patient population, and the study is ongoing, with further results expected to be reported at either the 2018 annual meeting of the American Society of Hematology or the 2019 annual meeting of the American Society of Clinical Oncology, Dr. Niemann said.
The study is supported by AbbVie and Janssen, which supplied the drugs and had the right to comment on the presentation. Dr. Niemann has previously disclosed consultancy fees from those companies and others.