Early Use of Fixed-Duration Venclexta-Rituxan Combo in Patients with Relapsed/Refractory CLL Effective, And Does Not Compromise Subsequent Therapy Response in Patients Who Need Retreatment

Five-year follow-up data of the MURANO trial presented at the 2020 American Society of Hematology Annual Meeting demonstrated that Venclexta (venetoclax) in combination with Rituxan (rituximab) to retreat patients with relapsed/refractory chronic lymphocytic leukemia (CLL) elicited a sustained time to next treatment benefit.

The data also demonstrated that treatment with the combination did not compromise response to subsequent therapy or overall survival (OS) rates.

“Five-year data from the MURANO study demonstrates that fixed duration (Venclexta)/(Rituxan) in patients with relapsed/refractory CLL demonstrates time-to-next treatment benefit, improved time to second progression-free survival event, and high response rates to subsequent therapies including re-exposure or cross-over to (Venclexta)-based regimens,” said lead author Dr. Rosemary Anne Harrup, a hematologist at Royal Hobart Hospital in Australia.

This analysis includes data regarding the response rates to follow-up treatment with Venclexta and Venclexta-based therapies, as well as exposure to Bruton tyrosine kinase inhibitor salvage therapy in patients who participated in the MURANO trial.

Study participants were randomized to receive either Venclexta and Rituxan or bendamustine and Rituxan during the initial phase of the MURANO trial. Investigator-assessed progression-free survival (PFS), which is the time from treatment to disease progression, was the main goal of the study. Patients in either arm whose disease progressed were followed for OS and disease response to any subsequent anti-CLL treatments.

At the time, the data demonstrated that six cycles of the Venclexta and Rituxan combination followed by fixed duration of treatment for a maximum of two years improved outcomes, compared with six cycles of the bendamustine and Rituxan combination.

“(Early efficacy data from MURANO) established (Venclexta) plus (Rituxan) as a standard of care for the treatment of patients relapsed/refractory CLL,” said Harrup.

An optional retreatment cross-over sub-study was added to the MURANO trial in 2018 to allow researchers to collect data from both the cross-over study and outside the cross over for patients who received either Venclexta-based treatments or a Bruton tyrosine kinase (BTK) inhibitor.

Time to next treatment (TTNT) more than doubled in those who received the Venclexta and Rituxan combination (194 patients) compared with those who treated with bendamustine and Rituxan (195 patients) with a median TTNT of 57.8 months versus 23.9 months, respectively.

At a median follow-up of 59 months, OS benefit was sustained among patients treated with the Venclexta combination. Five-year OS was 82.1% in patients who received the Venclexta combination compared with 62.2% in those who received bendamustine and Rituxan.

This study of retreated patients was launched because of the limited data available to guide subsequent therapies when relapse occurs after fixed duration Venclexta and Rituxan and uncertainty regarding the efficacy of repeated treatment with this combination.

After a median treatment-free interval of 23.7 months, 32 patients who received the Venclexta and Rituxan combination were re-treated with Venclexta-based regimens; 21 were enrolled in the re-treatment arm of the MURANO sub-study and 11 were treated outside of the sub-study.

Following disease progression, 67 patients treated with Venclexta and Rituxan and 123 patients treated with bendamustine and Rituxan received subsequent treatment. Data for patients subsequently treated with a BTK inhibitor or a Venclexta-based regimen were included in the presentation.

Eighteen patients in the Venclexta and Rituxan arm received treatment with a Bruton tyrosine kinase inhibitor, compared with 72 patients in the bendamustine and Rituxan arm. The Venclexta and Rituxan combination conferred a partial response or partial nodal response in 92.9% of patients, and the remaining 7.1% of patients had a complete response or complete response with incomplete bone marrow recovery. The response rates for patients in the bendamustine and Rituxan arm were 67.9% and 16.1%, respectively.

In total, 32 patients from the Venclexta and Rituxan arm and 15 patients from the bendamustine and Rituxan arm went on to receive Venclexta-based therapy and had 18 and 10 responders, respectively. The best overall response rate was 72.2% for those previously treated with Venclexta and Rituxan versus 80% for those previously treated with bendamustine.

Some patients (5.6%) who were in the Venclexta and Rituxan arm and received subsequent Venclexta-based treatment experienced a complete response or complete response with incomplete bone marrow recovery. More than half of the patients (66.7%) in the Venclexta and Rituxan arm who went on to receive subsequent Venclexta-based treatments experienced a partial response or partial nodal response to the therapy.

“This indicates that early use of (Venclexta)/(Rituxan) over bendamustine/(Rituxan) does not compromise efficacy of subsequent therapy,” Harrup said.

Of note, of the remaining patients in the Venclexta and Rituxan cohort, 22.4% of patients received subsequent chemoimmunotherapy and 3% received another unidentified therapy. In the bendamustine and Rituxan cohort, 19.5% of patients received chemoimmunotherapy and 9.8% received another therapy.

No new safety data was included in the presentation.

A version of this story appeared on OncLive® as “Venetoclax/Rituximab Combo Demonstrates Sustained Benefit for Retreated Patients with CLL.”

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