Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab.

Abstract

The MURANO trial (A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia [CLL]; ClinicalTrials.gov identifier #NCT02005471) reported superior progression-free survival (PFS) and overall survival (OS) with venetoclax-rituximab (VenR) vs bendamustine-rituximab (BR) in relapsed/refractory (R/R) CLL. Patients were randomized to 2 years of VenR (n = 194; rituximab for the first 6 months) or 6 months of BR (n = 195). Although undetectable minimal residual disease (uMRD) was achieved more often with VenR, the long-term implications of uMRD with this fixed-duration, chemotherapy-free regimen have not been explored. We report MRD kinetics and updated outcomes with 5 years' follow-up. Survival benefits with VenR vs BR were sustained (median PFS [95% confidence interval]: 53.6 [48.4, 57.0] vs 17.0 [15.5, 21.7] months, respectively, P < .0001; 5-year OS [95% confidence interval]: 82.1% [76.4, 87.8] vs 62.2% [54.8, 69.6], P < .0001). VenR was superior to BR, regardless of cytogenetic category. VenR-treated patients with uMRD at end of treatment (EOT; n = 83) had superior OS vs those with high-MRD+ (n = 12): 3-year post-EOT survival rates were 95.3% vs 72.9% (P = .039). In those with uMRD at EOT, median time to MRD conversion was 19.4 months. Of 47 patients with documented MRD conversion, 19 developed progressive disease (PD); median time from conversion to PD was 25.2 months. A population-based logistic growth model indicated slower MRD median doubling time post-EOT with VenR (93 days) vs BR (53 days; P = 1.2 × 10-7). No new safety signals were identified. Sustained survival, uMRD benefits, and durable responses support 2-year fixed-duration VenR treatment in R/R CLL.

• Authors: John F Seymour, Thomas J Kipps, Barbara F Eichhorst, James D'Rozario, Carolyn J Owen, Sarit Assouline, Nicole Lamanna, Tadeusz Robak, Javier de la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Clemens Mellink, Brenda Chyla, Anesh Panchal, Tong Lu, Jenny Q Wu, Yanwen Jiang, Marcus Lefebure, Michelle Boyer, Arnon P Kater
• Journal: Blood (Blood) Vol. 140 Issue 8 Pg. 839-850 (08 25 2022) ISSN: 1528-0020 [Electronic] United States
• PMID: 35605176 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology.

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Sulfonamides
• Rituximab
• Bendamustine Hydrochloride
• venetoclax

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Bendamustine Hydrochloride (adverse effects)
• Bridged Bicyclo Compounds, Heterocyclic (adverse effects)
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell
• Neoplasm, Residual (drug therapy, etiology)
• Recurrence
• Rituximab (adverse effects)
• Sulfonamides