TY - JOUR
T1 - Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab
AU - Seymour, John F.
AU - Kipps, Thomas J.
AU - Eichhorst, Barbara F.
AU - D'Rozario, James
AU - Owen, Carolyn J.
AU - Assouline, Sarit
AU - Lamanna, Nicole
AU - Robak, Tadeusz
AU - de la Serna, Javier
AU - Jaeger, Ulrich
AU - Cartron, Guillaume
AU - Montillo, Marco
AU - Mellink, Clemens
AU - Chyla, Brenda
AU - Panchal, Anesh
AU - Lu, Tong
AU - Wu, Jenny Q.
AU - Jiang, Yanwen
AU - Lefebure, Marcus
AU - Boyer, Michelle
AU - Kater, Arnon P.
N1 - Funding Information: Ven is being developed in a collaboration between Genentech, Inc. and AbbVie. Genentech, Inc. and AbbVie provided financial support for the study and participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. Third-party medical writing assistance under the direction of A.P.K. and J.F.S. was provided by Sinéad Holland and Simon Lancaster of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann–La Roche Ltd. Funding Information: The authors thank the patients and their families and all MURANO study team members and investigators. Special thanks are offered to Rosemary Harrup, Naomi Chang, Othman Al-Sawaf, Kirsten Fischer, and Can Zhang for their contributions. Ven is being developed in a collaboration between Genentech, Inc. and AbbVie. Genentech, Inc. and AbbVie provided financial support for the study and participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. Third-party medical writing assistance under the direction of A.P.K. and J.F.S. was provided by Sinéad Holland and Simon Lancaster of Ashfield MedComms, an Ashfield Health company, and was funded by F. Hoffmann–La Roche Ltd. Publisher Copyright: © 2022 American Society of Hematology
PY - 2022/8/25
Y1 - 2022/8/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85136528296&partnerID=8YFLogxK
U2 - https://doi.org/10.1182/blood.2021015014
DO - https://doi.org/10.1182/blood.2021015014
M3 - Article
C2 - 35605176
SN - 0006-4971
VL - 140
SP - 839
EP - 850
JO - Blood
JF - Blood
IS - 8
ER -