Clinical trialPhase 3Blood cancers (leukaemia, lymphoma and myeloma)Leukaemia

The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL

Blood · 2025389 patients (194 VenR, 195 BR)

Kater AP, Harrup R, Kipps TJ, Eichhorst B, Owen CJ, Assouline S, et al. Blood. 2025. 145:2733-2745

Study type: Clinical trial
Study name: MURANO
Phase: Phase 3
Design: Final analysis of a randomised trial (median follow-up 7 years) with a retreatment/crossover substudy
Sample size: 389 patients (194 VenR, 195 BR)
Source: Blood · 2025
Trial registration: NCT02005471

In plain words

In CLL that has come back, two years of venetoclax tablets together with 6 months of rituximab infusions kept the disease under control for a typical 4 and a half years (compared with about 1 and a half years with chemo-immunotherapy), and seven years after starting treatment 70% of patients were alive compared with 51%. If the disease came back again, retreatment with the same combination also worked in many patients.

Key results

54.7 vs 17.0 months

Median progression-free survival

Seven-year PFS with VenR 23.0%

69.6% vs 51.0%

Seven-year overall survival

Drugs in this study:Bendamustine Rituximab (Rituxan/MabThera)Venetoclax (Venclexta)

Dose and schedule cards

Venetoclax + rituximab (MURANO)

Relapsed or refractory CLLCycle length: Every 28 daysOn the page “Leukaemia” · Regimens and dosing in CLL: fixed-duration targeted therapy

Relapsed or refractory CLL

Drug	Dose	Route	Schedule
5-week ramp-up
Venetoclax	20, 50, 100, 200 and then 400 mg (one step each week)	Oral, with food	Weeks 1–5
After 7 days of venetoclax 400 mg (6 cycles)
Rituximab	375 mg/m² in cycle 1; 500 mg/m² in cycles 2–6	IV	Day 1 of each cycle
Continuation
Venetoclax	400 mg once daily	Oral	24 months from Day 1 of rituximab cycle 1

Cycle length: Every 28 days
Duration: Venetoclax 24 months (after the ramp-up); rituximab 6 cycles

TLS prophylaxis, CYP3A interactions and hepatitis B screening as in “Shared safety points” above.

On the page “Leukaemia” · Regimens and dosing in CLL: fixed-duration targeted therapy

Venetoclax + rituximab (MURANO)

Relapsed or refractory CLL/SLLCycle length: Every 28 daysOn the page “Venetoclax (Venclexta)” · Dose and schedule (FDA label)

Relapsed or refractory CLL/SLL

Drug	Dose	Route	Schedule
5-week ramp-up
Venetoclax	Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg	Oral, with food and water	Once a day
After 7 days of venetoclax 400 mg
Rituximab	Cycle 1: 375 mg/m²; cycles 2 to 6: 500 mg/m²	IV	Day 1, 6 cycles

Cycle length: Every 28 days
Duration: Venetoclax for 24 months from day 1 of rituximab cycle 1

On the page “Venetoclax (Venclexta)” · Dose and schedule (FDA label)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Venetoclax + rituximab (VenR)

Venetoclax after a 5-week ramp-up (20 mg with weekly increases) at 400 mg daily for 2 years + rituximab monthly for 6 months (375 mg/m² in cycle 1 and 500 mg/m² in cycles 2 to 6).

2Bendamustine + rituximab (BR)

Bendamustine 70 mg/m² on days 1 and 2 + rituximab (375 then 500 mg/m²) for 6 cycles of 28 days.

Source of the regimen details: Full text of the Blood 2025 paper in PMC (PMC12824681) and ClinicalTrials.gov NCT02005471 (doses)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with relapsed or refractory CLL after 1 to 3 prior lines of therapy including at least one chemotherapy-containing regimen; ECOG 0 or 1.

Endpoints

Progression-free survival and overall survival; minimal residual disease (MRD) at end of treatment; outcomes of retreatment or crossover with VenR.

Safety and side effects

No new safety findings were observed.

Clinical significance and place in guidelines

The final seven-year analysis confirmed a sustained overall survival benefit of fixed-duration VenR in relapsed or refractory CLL and showed that retreatment with VenR after relapse is feasible and effective.

Limitations

The comparator was chemo-immunotherapy; the number of patients in the retreatment substudy was small.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.