Ibrutinib Combined with Venetoclax for First-Line Treatment of CLL and SLL

CAPTIVATE is a study for patients aged 70 years or younger with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients enrolled in the study received ibrutinib alone (monotherapy) followed by ibrutinib plus venetoclax for a total of 15 cycles (approximately 15 months). Response to treatment was measured by testing for minimal residual disease (MRD) in the blood after 6, 9, and 12 cycles of ibrutinib plus venetoclax. Testing of MRD in bone marrow was done after 12 cycles of ibrutinib plus venetoclax.

A total of 164 patients participated in the study. Their median age was 58 years. Of those patients, 152 (93%) completed all 12 cycles of therapy. Almost all patients (97%) who received ibrutinib plus venetoclax responded. With a median follow-up of 15 months, 3 patients (2%) had disease progression, and none of the patients died.

Undetectable minimal residual disease (uMRD) was achieved in 74% of patients based on blood testing. The percentage of patients who had uMRD in blood increased over time, from 57% after 6 cycles of ibrutinib plus venetoclax to 73% after 12 cycles of ibrutinib plus venetoclax.

During treatment with ibrutinib alone, the most common side effects were diarrhea (31%) and joint pain (22%). Diarrhea (60%), low white blood-cell count (40%), nausea (34%), upper respiratory tract infection (24%), and fatigue (20%) were common during treatment with both drugs, ibrutinib plus venetoclax. Severe side effects leading to discontinuation of treatment were rare, with ibrutinib at 5% and venetoclax at 4%.

Researchers concluded that first-line treatment with ibrutinib plus venetoclax is an effective and safe chemotherapy-free regimen. This combination provides high rates of response, including uMRD. The safety profile of ibrutinib plus venetoclax was similar to known side effects for both agents.

Additional data from the CAPTIVATE study are still being collected. These data are expected to show that time-limited treatment with 12 cycles of ibrutinib plus venetoclax is possible.

Abstract 35. ASH 2019.