A combination of Venclexta (venetoclax) and rituximab continues to significantly reduce the risk of disease progression or death in relapsed or refractory chronic lymphocytic leukemia (CLL) patients two years after completing treatment, data from a Phase 3 clinical trial show.
“In the four-year analysis from the MURANO trial, treatment with the [Venclexta] combination resulted in an 81 percent reduction in the risk of progression or death compared to the standard of care,” John Seymour, PhD, the trial’s lead investigator, said in a press release. Seymor is also director of the hematology department at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital in Australia.
In addition, particularly durable responses were seen in patients with undetectable minimal residual disease (MRD) — fewer than one cancer cell in every 10,000 white blood cells in the blood or bone marrow — supporting MRD-negativity as a predictor of better treatment response and survival.
Data were presented in an oral presentation, “Four-Year Analysis of Murano Study Confirms Sustained Benefit of Time-Limited Venetoclax-Rituximab (VenR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL),” at the 61st American Society of Hematology Annual Meeting & Exposition, held recently in Orlando Florida.
Venclexta plus rituximab (sold as Rituxan and Truxima, among others) was the first oral, chemotherapy-free combination therapy approved by the U.S. Food and Drug Administration to treat CLL that gave patients an option for a fixed treatment duration, allowing them to stop treatment after nearly two years.
This approval was based on two-year data from the Phase 3 MURANO trial (NCT02005471), where the Venclexta-Rituxan combination was superior to standard chemoimmunotherapy — bendamustine plus rituximab — in halting disease progression and extending the survival of people with relapsed or refractory CLL.
Clinical benefits of the Venclexta combination compared with standard therapy were also observed in treatment response rate and MRD-negativity.
MURANO involved 389 CLL patients who had received at least one previous therapy. Participants were randomly assigned to receive either Venclexta (marketed by AbbVie and Genentech) for up to two years along with rituximab for the first six months, or standard chemoimmunotherapy for six months.
MURANO’s four-year data, which corresponds to approximately two years after the end of the combination treatment, shows that Venclexta continued to be superior to standard treatment in progression-free survival (PFS) — or the time a patient lives without signs of disease progression — overall survival, complete responses, and MRD-negativity two years after treatment.
People treated with the Venclexta combination had an 81% reduced risk of disease progression or death, with 57.3% of them still living with no signs of disease progression after four years, compared with 4.6% of patients in the standard therapy group.
In addition, significantly more patients in the combination therapy group (85.3%) were alive at four years, compared with those who received the standard treatment (66.8%), representing a 59% reduction in the risk of death. These benefits were seen despite 79% of patients in the standard therapy group receiving an additional targeted CLL therapy after disease progression.
Among the 64% of patients who had achieved MRD-negativity after combination therapy, 87% of them remained free of disease progression two years after treatment.
The previously reported association between undetectable MRD and improved PFS was maintained for both groups two years post-treatment, with patients with undetectable MRD living longer with no signs of disease progression than those with detectable MRD.
The safety profile of the Venclexta combo remained consistent with that of each individual therapy, with no new serious adverse events reported. Excluding non-melanoma skin cancer, one patient in the standard treatment group developed melanoma (a type of skin cancer), while two patients in the combination therapy group developed melanoma or breast cancer (one patient each).
“These results support the benefits of a fixed duration of treatment with [Venclexta] to reduce the risk of disease progression or death in patients with chronic lymphocytic leukemia,” said Mohammed Zaki, MD, PhD, AbbVie’s vice president and global head of hematology development.
“We remain committed to understanding the full utility of [Venclexta] combinations and to advancing other clinical development programs with the potential to transform the standards of care for patients with blood cancers,” he added.