Murano trial, ven+R vs BR

Background

Phase III open-label RCT enrolling 389 patients with relapsed or refractory CLL who had received 1-3 prior therapies (including ≥1 chemotherapy regimen), randomized 1:1 to a fixed-duration venetoclax-based regimen versus chemoimmunotherapy.

Interventions and follow up

Arm A: Venetoclax (5-week ramp-up 20→400mg, continued for 2 years) + rituximab x6 cycles
Arm B: Bendamustine + rituximab x6 cycles
Primary endpoint: Investigator-assessed PFS
mFollow up: 23.8mo

Results

24-mo PFS rate: 84.9% vs 36.3%, arm A vs B; HR 0.17, 95%CI 0.11–0.25; P<.001
Overall response rate: 92.3% vs 72.3%, arm A vs B
24-mo OS rate: 91.9% vs 86.6%, arm A vs B
Undetectable MRD (peripheral blood): markedly higher with venetoclax-rituximab

Adverse events

Hematologic/cytopenias: Grade 3-4 neutropenia 57.7% vs 38.8%; anemia 10.8% vs 13.8%; thrombocytopenia 5.7% vs 10.1%, arm A vs B
Infections/febrile neutropenia: Grade 3-4 infections 17.5% vs 21.8%; febrile neutropenia 3.6% vs 9.6%; overall grade 3-4 events 82.0% vs 70.2% (arm A vs B)

Conclusions

Fixed-duration venetoclax + rituximab produced significantly superior PFS and higher response and undetectable-MRD rates than bendamustine-rituximab in relapsed/refractory CLL.

Key Limitations

Open-label design; bendamustine-rituximab comparator less relevant in the BTK-inhibitor era; tumor lysis risk requires structured ramp-up; trial predates routine prior targeted-agent exposure, limiting generalizability to BTKi-refractory disease.

Clinical Context

Led to FDA/EMA approval of fixed-duration venetoclax + rituximab for relapsed/refractory CLL. ESMO/iwCLL guidelines endorse venetoclax-rituximab as a preferred time-limited option in the relapsed setting; longer follow-up confirmed durable PFS after treatment completion.

References