Analyses of Phase III MURANO study of Venclexta plus Rituxan show continued benefit in chronic lymphocytic leukemia.- Genentech/Roche.

Two new analyses of the Phase III MURANO study in people with previously treated chronic lymphocytic leukemia (CLL) demonstrated the continued clinical benefit of Venclexta (venetoclax) from Genentech/Roche, plus Rituxan (rituximab) was sustained after patients completed the chemotherapy-free, two-year fixed-duration course of therapy. An analysis showed the combination reduced the risk of disease progression or death (progression-free survival; PFS, as assessed by investigator) by 84 percent compared to standard of care bendamustine plus Rituxan (BR) after a median three-year follow-up. At three years, 71 percent of patients in the Venclexta plus Rituxan arm had not experienced disease progression, compared to 15 percent of patients in the BR arm (median PFS: not reached vs. 17.0 months, respectively). A clinically meaningful benefit in overall survival was also observed in the Venclexta arm compared to the BR arm (88 percent vs. 80 percent). Consistent benefit was observed in all patient subgroups for Venclexta plus Rituxan compared to BR, including high-risk and low-risk groups.

A separate analysis showed higher rates of minimal residual disease (MRD)-negativity observed with Venclexta plus Rituxan compared to BR were sustained after patients completed treatment (62 percent vs. 13 percent). MRD-negativity means no cancer can be detected using a specific, highly sensitive test, and was defined as less than 1 CLL cell in 10,000 leukocytes. Importantly, these results were observed in the majority of patients in the Venclexta arm, including patients in high-risk subgroups and were consistent with the maintained PFS benefit seen with longer follow-up. These data support the utility of MRD in peripheral blood as a predictive marker of clinical outcome. No new safety signals were observed with the treatment combination of Venclexta plus Rituxan. Data will be featured at the 60th American Society of Hematology (ASH) 2018 Annual Meeting.

Comment: Venclyxto was previously granted conditional marketing authorisation in the EU in December 2016 as a single agent for the treatment of CLL in the presence of 17p deletion or TP53 mutation in people who are unsuitable for or have failed a B-cell receptor pathway inhibitor. The EU approval in November 2018 follows the FDA approval in June 2018 of Venclexta in combination with Rituxan for the treatment of people with CLL or small lymphocytic lymphoma, with or without 17p deletion, who have received at least one prior therapy. Additional submissions of the MURANO data to health authorities around the world are ongoing.