Minimal residual disease-driven treatment intensification with sequential addition of ibrutinib to venetoclax in R/R CLL

This phase 2, multicenter study used a measurable residual disease (MRD)-driven approach to personalize intensity and duration of treatment for individual patients with relapsed/refractory CLL. Patients received venetoclax monotherapy for 12 cycles, and if Cycle 12 Day 1 MRD analysis to the level of 10(-4) was positive, ibrutinib was layered in. MRD was assessed every 3 cycles, and patients discontinued therapy if they demonstrated either a complete or partial response and undetectable MRD at any point in time from cycle 12 onward. Of 38 patients, one-third of whom had TP53 aberrations, 33 (87%) demonstrated undetectable MRD at some point in treatment. After a median follow-up of 36.5 months, median progression-free survival was not reached, and 10 patients experienced disease progression. After 3 years of follow up, 7 of 32 patients continued to demonstrate undetectable MRD. The most common grade 3-4 adverse event was neutropenia. Therefore, the authors concluded that this MRD-guided approach to intensification of therapy in the setting of relapsed/refractory CLL warrants further study.