The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia
Petra Langerbeins, Can Zhang, Sandra Robrecht, Paula Cramer, Moritz Fürstenau, Othman Al-Sawaf, Julia von Tresckow, Anna-Maria Fink, Karl-Anton Kreuzer, Ursula Vehling-Kaiser, Eugen Tausch, Lothar Müller, Michael Josef Eckart, Rudolf Schlag, Werner Freier, Tobias Gaska, Christina Balser, Marcel Reiser, Martina Stauch, Clemens-Martin Wendtner, Kirsten Fischer, Stephan Stilgenbauer, Barbara Eichhorst, Michael Hallek, Petra Langerbeins, Can Zhang, Sandra Robrecht, Paula Cramer, Moritz Fürstenau, Othman Al-Sawaf, Julia von Tresckow, Anna-Maria Fink, Karl-Anton Kreuzer, Ursula Vehling-Kaiser, Eugen Tausch, Lothar Müller, Michael Josef Eckart, Rudolf Schlag, Werner Freier, Tobias Gaska, Christina Balser, Marcel Reiser, Martina Stauch, Clemens-Martin Wendtner, Kirsten Fischer, Stephan Stilgenbauer, Barbara Eichhorst, Michael Hallek
Abstract
Observation is the current standard of care for patients with early-stage asymptomatic chronic lymphocytic leukemia (CLL), as chemotherapy-based interventions have failed to prolong survival. We hypothesized that early intervention with ibrutinib would be well tolerated and lead to superior disease control in a subgroup of early-stage patients with CLL. The phase 3, double-blind, placebo-controlled CLL12 trial randomly assigned asymptomatic, treatment-naïve Binet stage A CLL patients at increased risk of progression in a 1:1 ratio to receive ibrutinib (n = 182) or placebo (n = 181) at a dose of 420 mg daily. At a median follow-up of 31 months, the study met its primary endpoint by significantly improving event-free survival in the ibrutinib group (median, not reached vs 47.8 months; hazard ratio = 0.25; 95% confidence interval = 0.14-0.43, P < .0001). Compared with placebo, ibrutinib did not increase overall toxicity, yielding similar incidence and severity of adverse events (AEs). The most common serious AEs were atrial fibrillation, pneumonia, and rash in the ibrutinib group, and basal cell carcinoma, pneumonia, and myocardial infarction in the placebo group. Ibrutinib-associated risk for bleeding (33.5%) was decreased by prohibiting the use of oral anticoagulants through an amendment of the study protocol and by avoiding CYP3A4 drug-drug interactions. Ibrutinib confirms efficacy in CLL patients at an early stage with an increased risk of progression. However, the results do not justify changing the current standard of "watch and wait." This trial was registered at www.clinicaltrials.gov as #NCT02863718.
© 2022 by The American Society of Hematology.
Source: PubMed