Six-year follow-up and subgroup analyses of a phase 2 trial of venetoclax for del(17p) chronic lymphocytic leukemia

Stilgenbauer, S; Tausch, E; Roberts, AW; Davids, MS; Eichhorst, B; Hallek, MJ; Hilmen, P; Schneider, C; Schetelig, J; B&#246;ttcher, S; Kater, AP; Jiang, Y; Boyer, M; Popovic, R; Ghanim, MT; Moran, M; Sinai, WJ; Wang, X; Mukherjee, N; Chyla, B; Wierda, WG; Seymour, JF

Author(s): Stilgenbauer, S; Tausch, E; Roberts, AW; Davids, MS; Eichhorst, B; Hallek, MJ; Hilmen, P; Schneider, C; Schetelig, J; Böttcher, S; Kater, AP; Jiang, Y; Boyer, M; Popovic, R; Ghanim, MT; Moran, M; Sinai, WJ; Wang, X; Mukherjee, N; Chyla, B; Wierda, WG; Seymour, JF;
Details: Publication Year 2024-01-30,Volume 8,Issue #8,Page 1992-2004
Journal Title: Blood Advances
Abstract: Chromosome 17p deletion (del[17p]) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). Venetoclax is approved for treatment of previously untreated and relapsed/refractory (R/R) CLL, including patients with del(17p), based on the open-label, multicenter, phase 2 M13-982 trial (NCT01889186). Here, we detail the 6-year follow-up analysis for M13-982. A total of 158 patients with previously untreated (n = 5) or R/R (n = 153) del(17p) CLL received 400 mg venetoclax daily after initial ramp-up until progressive disease. After a median follow-up of 70 months, the best objective response rate (ORR) was 77% (21% complete remission [CR], 49% partial remission [PR]), with a median duration of response (DOR) of 39.3 months (95% confidence interval [CI], 31.1-50.5). The median progression-free survival (PFS) was 28.2 months (95% CI, 23.4-37.6), median overall survival (OS) was 62.5 months (95% CI, 51.7-not reached), with 16% of patients remaining on treatment after 6 years. Multivariable analysis did not identify statistically significant correlation between patient subgroups defined by clinical or laboratory variables and ORR or PFS. The most common grade ≥3 adverse events were neutropenia (42%), infections (33%), anemia (16%), and thrombocytopenia (16%). Post hoc comparative analyses of PFS and OS from treatment initiation, from a 24-month landmark, and by minimal residual disease status were performed between patients with del(17p) in M13-982 and MURANO in the interest of understanding these data in another context. These long-term data show the continued benefits of venetoclax in patients with del(17p) CLL.
Publisher: ASH
Keywords: Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/genetics; Follow-Up Studies; Bridged Bicyclo Compounds, Heterocyclic/adverse effects; Sulfonamides/adverse effects; Recurrence; Chromosome Deletion
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 38290108
Publisher's Version: https://doi.org/10.1182/bloodadvances.2023011741
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2023011741
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-29 09:02:03

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