Assessment of the Clonal Dynamics of Acquired Mutations in Patients (Pts) with Relapsed/Refractory Chronic Lymphocytic Leukemia (R/R CLL) Treated in the Randomized Phase 3 Murano Trial Supports Venetoclax-Rituximab (VenR) Fixed-Duration Combination Treatment (Tx)

Introduction: In the MURANO trial (NCT02005471), fixed-duration VenR (2 yrs Ven + R for the first 6 mo) improved survival and rates of undetectable minimal residual disease (MRD) over bendamustine (Benda)-R in pts with R/R CLL. Novel recurrent mutations in BCL2 and family genes (eg BAX and PMAIP1 [encoding Noxa]) have been linked to Ven resistance. We analyzed MRD+ samples from VenR-treated pts in MURANO to assess the nature and frequency of acquired mutations in BCL2 family genes (marker of emergent Ven resistance) and TP53 (may negatively impact response to re-Tx). We also analyzed the impact of these mutations on time to next CLL Tx (TTNT) and subsequent response.