The multinational, open-label, phase 3 CLL14 trial was designed to compare fixed-duration targeted venetoclax plus obinutuzumab (VenG) treatment versus chlorambucil plus obinutuzumab (ClbG) treatment in previously untreated patients with chronic lymphocytic leukemia (CLL) and comorbidities. At the ASCO 2019 Annual Meeting, researchers presented end point analyses, including progression-free survival (PFS) and minimal residual disease (MRD) negativity.
Eligible patients had a Cumulative Illness Rating Scale score >6 and/or an estimated creatinine clearance of <70 mL/min. These patients were randomized 1:1 to receive either chlorambucil 0.5 mg/kg on day 1 and day 15 or 400-mg venetoclax (after 5-week ramp-up) for 12 cycles of equal duration in combination with obinutuzumab for the first 6 of the 12 cycles. The primary study end point was PFS, and a key secondary end point was MRD-negative status, which was assessed in peripheral blood or bone marrow 3 months after treatment completion.
A total of 432 patients were enrolled in the trial; 216 in each treatment group. Of the patients, 85% responded to VenG (50% complete response [CR]), compared with 71% response to ClbG (23% CR). After 28 months of median follow-up, superior PFS was observed with VenG versus ClbG (hazard ratio, 0.35; 95% confidence interval, 0.23-0.53; P <.001). MRD negativity was significantly higher with VenG versus ClbG in both peripheral blood (76% vs 35%; P <.001) and bone marrow (57% vs 17%; P <.001) 3 months after treatment completion. There was a low rate of conversion to MRD-positive status 12 months after treatment.
Researchers concluded that fixed-duration VenG induced deep and durable MRD-negativity rates in previously untreated patients with CLL and comorbidities. These findings translated into improved PFS for patients participating in the trial. Although safety data were not reported in this analysis and must also be considered, these results may have important implications for frontline treatment of CLL.
Abstract 7502; Fischer K, et al.