Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Open accessAbstract
BACKGROUND: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. METHODS: 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 for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival. RESULTS: After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). 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 versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients). CONCLUSIONS: Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).
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In patients who have not previously received venetoclax, combination therapy with venetoclax and an anti-CD20 monoclonal antibody can achieve durable remissions in most cases.
“In patientswho have not previously received venetoclax, combination therapy with venetoclax and an anti-CD20 monoclonal antibody (mAb)can achieve durable remissions in most cases(54).”
From Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy (2025) · cites this paper as [54]
The Efficacy section reports 84.9% progression-free survival at two years with venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia, supporting benefit in most patients. But the Discussion says additional follow-up was needed to assess durability after treatment stopped. The paper studies rituximab specifically, and the available Patients section does not establish that all participants were previously untreated with venetoclax. (LLM, conf=0.86)
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Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy
Gruessner, C., Wiestner, A., & Sun, C. (2025) · Leukemia & Lymphoma · doi:10.1080/10428194.2025.2466101 · Cited by 6 · see citing works
“Prior treatment status with venetoclax should also be factored into decisions. in patients who have not previously received venetoclax, combination therapy with venetoclax and an anti-cD20 monoclonal antibody (mAb) can achieve durable remissions in most cases [53].”
- Authors
- Seymour, J. F., Kipps, T. J., Eichhorst, B., Hillmen, P., D’Rozario, J., Assouline, S., Owen, C., Gerecitano, J., Robak, T., De la Serna, J., Jaeger, U., Cartron, G., Montillo, M., Humerickhouse, R., Punnoose, E. A., Li, Y., Boyer, M., Humphrey, K., Mobasher, M., & Kater, A. P.
- Affiliations
- Australian National University (AU)
- From the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) — all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) — both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne–Bonn, Cologne, Germany (B.E.); St....
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-03-22
- Volume
- 378
- Issue
- 12
- Pages
- 1107-1120
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2792666902
- Cited by
- 940
- References
- 2
- Citations by year
- 2026: 60 · 2025: 79 · 2024: 104 · 2023: 109 · 2022: 123 · 2021: 144 · 2020: 133 · 2019: 132 · 2018: 53 · 2017: 1 · 2013: 1
- FWCI
- 65.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL Portal Artxiker (Hindustan Aeronautics Limited (India)) (submittedVersion)
- HAL (submittedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- F. Hoffmann La-Roche Ltd
- AbbVie Inc.
- Topics
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- venetoclax, rituximab, chronic lymphocytic leukemia, relapsed/refractory disease, BCL-2 inhibition, bendamustine, progression-free survival, chromosome 17p deletion, combination therapy, targeted therapy, survival outcomes, adverse events, relapse after treatment discontinuation
- MeSH terms
- Rituximab, Bendamustine Hydrochloride, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Male, Middle Aged, Neutropenia, Recurrence, Sulfonamides, Tumor Lysis Syndrome, Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasm, Residual, Disease-Free Survival, Drug Resistance, Neoplasm, Bridged Bicyclo Compounds, Heterocyclic, Kaplan-Meier Estimate, Young Adult
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