Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma:…CLL/SLL with del(17p)/TP53 mutation…Preferred regimens...Venetoclax + rituximab

In the VenR cohort, uMRD at EOT is associated with improved OS. Unmutated IGVH, del(17p) and GC (≥3 CNV) are associated with higher rates of MRD conversion and subsequent PD after attaining uMRD at EOT. Overall, a substantial proportion of pts who completed Ven Tx retained uMRD 36 mo after treatment cessation, displaying durable response following 2-yr fixed-duration VenR.

Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR….Of 389 patients, 194 were assigned to VenR and 195 to BR....In the VenR arm, a significant impact of del(17p) on PFS (P < .01) was seen in patients with high-GC status but not patients with low-GC status or noncomplex GC.

MURANO demonstrated significant PFS benefit for venetoclax + rituximab (VenR) given for a fixed duration vs bendamustine + rituximab (BR) in relapsed/refractory (R/R) CLL. Here we present analysis of peripheral blood (PB) MRD kinetics in relation to PFS in MURANO with long follow up, when all pts have completed therapy. VenR pts achieved high PB uMRD rates...Consistently high uMRD rates were observed in all VenR subgroups, including pts with high-risk cytogenetics and molecular factors: del(17p) and/or TP53 mutated…

Patients with both del(17p) and TP53 mutations, indicative of loss of TP53 on both alleles, had inferior outcomes to pts with either del(17p) or TP53 mutation alone, with BR. Importantly, PFS was superior for VenR vs BR across subgroups with del(17p) and/or TP53 mutations including high and low clone size.

In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab… The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group...

Adult patients with CLL requiring therapy treated with Ven+R according to local label are eligible for the study….The response rate in patients presenting with high risk features, e.g., del(17p), TP53 mutation or unmutated IGHV, was high.