CLL-045 The Dedalo Protocol: An Integrated Approach to MRD in CLL Patients Receiving Venetoclax Plus Rituximab.

BACKGROUND: In previous analyses, the MURANO study demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit for fixed-duration venetoclax-rituximab treatment compared with bendamustine-rituximab in relapsed/refractory chronic lymphocytic leukemia patients. Furthermore, the study demonstrated that deep responses with undetectable minimal residual disease (uMRD) were associated with favorable PFS. We designed the "Dedalo" study with the goal of testing MRD from a multidisciplinary point of view (flow cytometry, molecular biology and ultrasound) and of assessing MRD predictive/prognostic value.

METHODS: Today 17 patients have been enrolled in the protocol; most of them were characterized by IgHV mutational status and TP53/del(17p) presence. MRD status was assessed by flow cytometry in peripheral blood from 11 patients after the first cycle and in 10 patients after the sixth cycle of rituximab-venetoclax, with a sensitivity of 10-4 .

RESULTS: Out of the 17 enrolled patients, only one patient had to discontinue the treatment and 8 patients reached the twelfth month of therapy. After the first cycle, MRD status was assessed in 11 patients, with a 72.7% rate of PB undetectable MRD (less than 10-4 ) and a 27.3% rate of low MRD positivity, and with 0% of high MRD positivity (defined as ≥ 10-2 ). After the sixth cycle, conversely, MRD status was assessed in 10 patients, with an 80% rate of uMRD. Among the 5 patients carrying del(17p) or TP53 mutation, 3 patients reached uMRD after the first cycle, 1 patient has achieved a low MRD positivity after the first cycle, and 1 patient remained MRD positive after the eighteenth cycle.

CONCLUSIONS: With all patients still on treatment, favorable MRD kinetics was observed in the venetoclax-rituximab setting. The majority of patients achieved PB uMRD after the first cycle of the treatment, with a higher percentage after the sixth cycle. These results are superimposable to those from MURANO trial (at 4 months, uMRD 60%, low MRD positivity 20%, 78% at 6 months). The durability of uMRD rates, their role in the prediction of PFS in a real-life experience, and the effect of genetic characteristics on the MRD kinetics are still under investigation.