Venetoclax retreatment in chronic lymphocytic leukemia is biologically rational and clinically effective

Castonguay, M; Anderson, MA; Thompson, P; Seymour, JF

Author(s): Castonguay, M; Anderson, MA; Thompson, P; Seymour, JF;
Details: Publication Year 2026-05-26,Volume 10,Issue #10,Page 3357-3366
Journal Title: Blood Advances
Abstract: Venetoclax therapy has evolved from continuous monotherapy to fixed-duration (FD) and minimal residual disease (MRD)-guided combination regimens in frontline and relapsed/refractory chronic lymphocytic leukemia. Compared with continuous therapy, FD regimens are associated with a lower incidence of emergence of BCL2 mutations and distinct mechanisms of relapse, supporting the rationale for investigating venetoclax-based combination retreatment strategies. In this review, we summarize the key studies for venetoclax rechallenge and discuss the available clinical evidence. To date, 10 abstracts or published articles have reported on venetoclax retreatment, including continuous monotherapy or with FD/MRD-guided combinations with anti-CD20 monoclonal antibodies (rituximab and obinutuzumab) or covalent Bruton tyrosine kinase inhibitors (ibrutinib and acalabrutinib). Patient and disease characteristics were heterogeneous across studies, with a substantial proportion of patients with high-risk disease (IGHV-unmutated or del17p/TP53 mutations). The median time off venetoclax following initial therapy ranged from 9 to 90 months. The reported overall response rates to retreatment ranged from 72% to 100%, and undetectable MRD rates in peripheral blood from 32% to 92%. Median progression-free survival, when available, ranged from 23 to 58 months. Optimal patient selection remains to be defined, but the depth of the initial venetoclax response and time to progression from last venetoclax exposure may predict rechallenge efficacy and are incorporated in new clinical trial criteria allowing previous FD venetoclax treatment.
Publisher: ASH
Keywords: Humans; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/mortality; *Bridged Bicyclo Compounds, Heterocyclic/therapeutic use; *Sulfonamides/therapeutic use/pharmacology; Retreatment; *Antineoplastic Agents/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Treatment Outcome
Research Division(s): Blood Cells and Blood Cancer
PubMed ID: 41843779
Publisher's Version: https://doi.org/10.1182/bloodadvances.2026019871
Open Access at Publisher's Site: https://doi.org/10.1182/bloodadvances.2026019871.
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-05-14 03:10:43

Last Modified: 2026-05-14 03:10:54