Diving into the MURANO trial
Dr. Edward Crane reviews the R/R efficacy and safety results of the MURANO trial.
Edward Crane, MD
TriHealth Cancer Institute
Welcome. My name is Dr. Edward Crane. I am a hematologist oncologist at TriHealth Cancer Institute based in Cincinnati, Ohio. Thank you for joining me as I share with you an application of VENCLEXTA in relapsed or refractory chronic lymphocytic leukemia, or CLL, based on the data from the MURANO trial. VENCLEXTA is a BCL-2 inhibitor indicated 1 for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. 1 MURANO was a 1:1 randomized, multicenter, open-label, phase III trial that compared the efficacy and safety of VENCLEXTA + rituximab, VEN+R, with bendamustine + rituximab, BR, in patients with relapsed or refractory CLL who had received at least one line of prior therapy. 1 Rituximab and bendamustine were taken for six 28-day cycles, 1 and this is the standard 6 cycles of BR. 16 VENCLEXTA was initiated with a 5-week dose ramp-up schedule followed by 24 cycles of 400 mg/day.
This schedule was used to gradually reduce tumor burden and reduce the risk of tumor lysis syndrome, or TLS. 1 Tumor burden assessments, including radiographic evaluation and blood chemistry assessment, are recommended prior to VENCLEXTA initiation to assess the risk for TLS. 1 A total of 389 patients were enrolled. 194 and 195 patients were randomized to VEN+R and BR arms, respectively. 1 Here you can see some select inclusion criteria, as well as key study endpoints. The primary endpoint was progression-free survival, or PFS. 5 Baseline demographics and disease characteristics were generally well balanced between the treatment arms. 1
Let’s look at the primary efficacy readout from the MURANO trial. Overall, VEN+R demonstrated a durable PFS with 24 months of treatment, which was superior to patients treated with BR, a standard chemoimmunotherapy. 1,5 Specifically, after a median follow-up of over 23 months, treatment with VEN+R significantly decreased the risk of progression or death by 81%, and the estimated 24-month PFS was 83% for VEN+R vs 39% for BR. 1,8 The median PFS was not reached for VEN+R versus 18.1 months with BR. 1 An additional 48-month post hoc analysis examined investigator-assessed PFS after stopping treatment at about 24 months. 1,10 The estimated 48-month PFS was 57% in VEN+R, compared to 5% in the BR arm. 10 The estimated 18-month PFS post-treatment in patients who completed 24 months of VEN+R was 76%. 10 Among patients who received subsequent treatment, the majority of them were treated with either a BTK inhibitor or other treatment listed here with the associated response rates. 8
Safety was evaluated in 194 patients treated with VEN+R and in 188 BR-treated patients. 1 Here are the most common adverse reactions from table 11 of the Prescribing Information. 1 Neutropenia was the most common adverse reaction in both arms. Other adverse reactions such as diarrhea, upper and lower respiratory tract infection, and musculoskeletal pain tended to not have as high of an incidence of Grade 3 or greater adverse reactions. 1 After the study protocol was amended to implement the current TLS prophylaxis and monitoring measures, 0% incidence of clinical TLS was observed in MURANO. 1 Incidence of TLS occurred in 3% of patients treated with VEN+R overall. 1 All TLS events occurred during the ramp-up period and were resolved within 2 days. 1 All 6 patients completed the ramp-up and reached the recommended daily dose of 400 mg of VENCLEXTA. 1 Other adverse reactions at all grades reported in greater than or equal to 10% of patients in the VEN+R arm in MURANO and other important adverse reactions included fatigue at 22%, cough at 22%, nausea at 21%, and anemia at 16%, among others.1 AbbVie and Genentech would like to thank all of the patients and their families, investigators, and clinical study sites from across the country who were involved with the MURANO trial. I would also like to thank you for joining me in exploring the activity of the fixed duration VENCLEXTA + rituximab regimen for patients with R/R CLL.