Photo Credit: Nemes Laszlo
First-line, fixed-duration ibrutinib plus venetoclax provides durable progression-free survival (PFS) and overall survival (OS) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to results from the phase II CAPTIVATE study presented at the 66th American Society of Hematology Annual Meeting & Exposition.
The study explored baseline lymph node (LN) size, depth of LN and measurable residual disease (MRD) response, and outcomes. The researchers also evaluated response per International Working Group CLL criteria, undetectable MRD (uMRD4; <10–4 by flow cytometry), PFS, and overall survival (OS) efficacy outcomes in patient subgroups defined by maximal LN long diameter (LDi) at baseline and at the end of treatment (EOT) by performing post hoc exploratory analyses.
Patients aged 70 years and older with previously untreated CLL or SLL received three cycles of ibrutinib and 12 cycles of ibrutinib plus venetoclax. In the fixed duration cohort (n=159), oral ibrutinib was administered at 420 mg/day, and oral venetoclax was administered up to 400 mg/day in a five-week ramp-up. In the MRD cohort (n=43), patients received an additional cycle of ibrutinib plus venetoclax and were randomized to placebo.
At EOT, 65% of patients with baseline LDi less than 5 cm achieved high uMRD4 rates, and 77% patients with baseline LDi ≥5 cm achieved high uMRD4 rates. The complete response rates for each subgroup were 66% and 21%, respectively.
LDi ≤1.5 cm was achieved in 71% of patients with baseline LDi less than 5 cm and in 27% of patients with baseline LDi ≥5 cm. Meanwhile, LDi ≤2 cm was achieved in 89% of patients with baseline LDi less than 5 cm and in 54% of patients with baseline LDi ≥5 cm. Patients with EOT LDi ≤1.5 cm had uMRD4 rates of 71% in the peripheral blood and 72% in the bone marrow, and patients with EOT LDi ≤2 cm had uMRD4 rates of 69% in the peripheral blood and 70% in the bone marrow.
The 5.5-year PFS rates were comparable among patients with baseline LDi less than 5 (67%) and LDi ≥5 cm (63%). In addition, the OS was 97% in both cohorts. The PFS rates were also similar among patients with EOT LDi ≤1.5 (69%) or EOT LDi greater than 1.5 cm (64%) and EOT LDi ≤2 (67%) or EOT LDi greater than 2 cm (63%).
However, the PFS rates were higher among patients who achieved uMRD4 in the peripheral blood compared with those who had detectable MRD irrespective of LDi. For patients who achieved uMRD4, the PFS rates were 77% for EOT LDi ≤1.5 cm, 75% for EOT LDi between 1.5 and 2 cm, and 72% for EOT LDi greater than 2 cm. For those with detectable MRD, the PFS rates were 50% for EOT LDi ≤1.5 cm, 43% for EOT LDi between 1.5 and 2 cm, and 42% for EOT LDi greater than 2 cm. These rates corresponded with those for uMRD4 in the bone marrow versus detectable MRD. The researchers also noted that the PFS rates were higher among those with uMRD4 in the bone marrow regardless of iwCLL response category.
Sixty-four percent of patients with baseline LDi less 5 cm had treatment-emergent grade ≥3 adverse events (TEAEs), and 3% experienced AEs leading to discontinuation. Fifty-eight percent of patients with baseline LDi ≥5 cm had grade ≥3 TEAEs, and 6% experienced AEs leading to discontinuation.
