Venclyxto monotherapy is indicated for the treatment of chronic lymphocytic leukaemia (CLL) in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B cell receptor pathway inhibitor.

Venetoclax monotherapy is recommended, within its marketing authorisation, for treating chronic lymphocytic leukaemia (CLL) in adults...with a 17p deletion or TP53 mutation and when a B-cell receptor pathway inhibitor is unsuitable, or whose disease has progressed after a B-cell receptor pathway inhibitor.

Suggested treatment regimens...CLL/SLL with del(17p)/TP53 mutation…Relapsed/refractory therapy…preferred regimen…Venetoclax

Recommendations: TP53 mutation or del(17p): ibrutinib or acalabrutinib or venetoclax plus obinutuzumab or venetoclax alone or idelalisib plus rituximab [III, A].

This is an open-label, phase 3b, multicenter study (NCT02980731)…Patients were ≥18 years old with R/R CLL, including those with 17p deletion, TP53 mutations, and/or prior experience with B-cell receptor inhibitor-containing (BCRi) therapy, treated with Ven monotherapy....Clinically meaningful improvements in global health status, role functioning and fatigue were observed as early as week 12 post-treatment.

...Subjects must have 17p deletion, assessed by local laboratory (in bone marrow or peripheral blood) or assessed by central laboratory (peripheral blood)...To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. (Main Cohort)...To evaluate the efficacy of ABT-199 monotherapy in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. (Expanded Safety Cohort)...

CLL patients included in this study required therapy and were eligible for Ven monotherapy treatment according to local label.... the best ORR (CR/CRi) was 76% (43%) in patients with TP53 aberrations and 69% (27%) in patients without TP53 aberrations. When subdivided according to IGHV status, the best ORR (CR/CRi) was 83% (33%) in IGHV mutated...CR/CRi rates were highest in patients with TP53 aberration or IGHV unmutated patients.

Adults with R/R or previously untreated del(17p) CLL received Ven 400 mg (via ramp-up) orally daily until progressive disease (PD) or intolerance. At end of study (median f/u, 70 mo), 48% of pts were alive, 24% were progression-free, and 16% remained on Ven, confirming the long-term activity of Ven in this high-risk population with del(17p) CLL and median 2 prior LOT. mPFS was shorter in pts with mutated SF3B1 (n=28) vs without (n=109; 16.4 vs 30.2 mo [P=.0071]).

...8/33 (24%) carried del(17p); 10/30 (33%) TP53 mutations, and 24/30 (80%) unmutated IGHV….overall response rate with VEN mono was 36/38 (95%), 19 CR and 17 PR….

...Del(17p), 15.0%; TP53 mutation…In the 62 patients of the evaluable population, the 1-year ORR was 85.5% [95% CI 76.7% - 94.3%]. Considering the median follow-up of patients of 13.1 months, the 1-year estimate for PFS was 80.2% [95% CI 68.8% - 88.6%].... V monotherapy is effective in non-selected pre-treated CLL patients, with similar outcomes as compared to clinical trials.

We treated 34 pts with rapid venetoclax dose escalation. Median age at venetoclax start was 54 years old and were 73.5% men. Pts had a median of 5 previous CLL trtmts (range 2-18). The most recent trtmt was single-agent BCRi in 18 cases, which overlapped with venetoclax in the majority. Only 6 pts had high tumor burden and the majority had low or medium tumor burden. Cytogenetic abnormalities at venetoclax start included: 17 (50.0%) pts with 17p deletion, 5 (14.7%) with 13q deletion, 6 (17.6%) with 11q deletion, and 3 (8.8%) with trisomy 12. Fifty percent of pts had a complex karyotype, and 76.5% had unmutated IGVH status. 24 (80%, n=30 pts that had testing done) pts had confirmed BTK/PLCу2 mutations...Rapid dose escalation of venetoclax in this pt population is safe and feasible. Despite a high percentage of patients developing TLS (52.9%), all patients recovered without lasting complications and all but one were able to achieve the goal dose of venetoclax. This dosing scheme achieved disease control with 67.6% remaining progression-free at 1 year and the majority of pts surviving...

...this phase 2, single-arm, multicentre study, we recruited patients aged 18 years and older with del(17p) relapsed or refractory chronic lymphocytic leukaemia...At a median follow-up of 12·1 months (IQR 10·1-14·2), an overall response by independent review was achieved in 85 (79·4%; 95% CI 70·5-86·6) of 107 patients. Results of this trial show that venetoclax monotherapy is active and well tolerated in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia...