MURANO: trial | Bending the Curve: Trial by Trial

MURANO

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)

Phase 3N = 389NCT02005471

Population

Adults with relapsed or refractory CLL

Design

Open-label randomised phase 3: venetoclax for up to 2 years plus rituximab for the first 6 months versus bendamustine plus rituximab for 6 months. The original design had no crossover. The final analysis (median follow-up 7 years) also reports a substudy of venetoclax-rituximab retreatment or crossover at progression. ClinicalTrials.gov actual enrolment equals the 389 randomised.

Primary endpoint

PFS

Arms

Venetoclax-rituximab (experimental, n = 194): Venetoclax for up to 2 years plus rituximab for the first 6 months
Bendamustine-rituximab (control, n = 195): Bendamustine plus rituximab for 6 months

People

Seymour JF

PFSHR 0.17 (95% CI 0.11–0.25)Δ 24-month PFS+48.6 pointsPFSHR 0.13 (95% CI 0.05–0.29)Δ 24-month PFS+53.7 pointsPFSHR 0.23 (95% CI 0.18–0.29)Δ median PFS+37.7 months

Show the numbers

Results reported for MURANO
Endpoint	Analysis	Venetoclax-rituximab	Bendamustine-rituximab	Effect
PFSAll randomised patients (194 vs 195)	primarymedian follow-up 23.8 monthsSeymour 2018	84.9% at 2 y	36.3% at 2 y	HR 0.17 (95% CI 0.11–0.25)P<0.001Investigator-assessed progression-free survival; 32 events in 194 patients with venetoclax-rituximab versus 114 events in 195 with bendamustine-rituximab.
PFSPatients with chromosome 17p deletion	primarySeymour 2018	81.5% at 2 y	27.8% at 2 y	HR 0.13 (95% CI 0.05–0.29)Subgroup reported in the abstract.
PFSAll randomised patients (194 vs 195)	finalmedian follow-up 85.7 monthsKater 2025	median 54.7 months; 23% at 7 y	median 17 months	HR 0.23 (95% CI 0.18–0.29)P<0.0001Final analysis, data cut 3 August 2022; investigator-assessed PFS. No bendamustine-rituximab patient remained progression-free at 7 years (full text).
OSAll randomised patients (194 vs 195)	finalmedian follow-up 85.7 monthsKater 2025	69.6% at 7 y	51% at 7 y	HR 0.53 (95% CI 0.37–0.74)P=0.0002Seven-year overall survival at the final data cut; median OS not reached with venetoclax-rituximab vs 87.8 months with bendamustine-rituximab.

Results reported for MURANO
Endpoint	Analysis	Venetoclax-rituximab	Bendamustine-rituximab	Effect
PFSAll randomised patients (194 vs 195)	primarymedian follow-up 23.8 monthsSeymour 2018	84.9% at 2 y	36.3% at 2 y	HR 0.17 (95% CI 0.11–0.25)P<0.001Investigator-assessed progression-free survival; 32 events in 194 patients with venetoclax-rituximab versus 114 events in 195 with bendamustine-rituximab.
PFSPatients with chromosome 17p deletion	primarySeymour 2018	81.5% at 2 y	27.8% at 2 y	HR 0.13 (95% CI 0.05–0.29)Subgroup reported in the abstract.
PFSAll randomised patients (194 vs 195)	finalmedian follow-up 85.7 monthsKater 2025	median 54.7 months; 23% at 7 y	median 17 months	HR 0.23 (95% CI 0.18–0.29)P<0.0001Final analysis, data cut 3 August 2022; investigator-assessed PFS. No bendamustine-rituximab patient remained progression-free at 7 years (full text).
OSAll randomised patients (194 vs 195)	finalmedian follow-up 85.7 monthsKater 2025	69.6% at 7 y	51% at 7 y	HR 0.53 (95% CI 0.37–0.74)P=0.0002Seven-year overall survival at the final data cut; median OS not reached with venetoclax-rituximab vs 87.8 months with bendamustine-rituximab.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.17	0.11–0.25
PFS	0.13	0.05–0.29
PFS	0.23	0.18–0.29
OS	0.53	0.37–0.74

Illustrative — modelled from reported values, not trial data. PFS, final.

Show curves

Venetoclax-rituximab (experimental)
Bendamustine-rituximab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Venetoclax-rituximab	Bendamustine-rituximab
0	100.0%	100.0%
34	65.0%	25.0%
68	42.2%	6.3%
103	27.1%	1.5%
137	17.6%	0.4%

Appears in

2015 Venetoclax: BCL2 inhibition, from phase 1 to MURANO

Sources

Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, et al. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018;378(12):1107-1120.
PubMed DOI
Kater AP, Harrup R, Kipps TJ, Eichhorst B, Owen CJ, Assouline S, et al. The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL. Blood. 2025;145(23):2733-2745.
PubMed DOI