A combination of Venclexta (venetoclax) and Rituxan (rituximab) significantly reduces the risk of disease progression or death in relapsed or refractory chronic lymphocytic leukemia (CLL) patients, according to a Phase 3 clinical trial.
The study, “Venetoclax–Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia,” was published in The New England Journal of Medicine.
While the introduction of chemoimmunotherapy in the treatment of CLL improved the outcomes of first-line therapy, most patients still relapse and need additional therapy.
Genetic deletions in chromosome 17 (called the 17p deletion) are highly associated with unfavorable outcomes with standard CLL therapies, and are found in up to 50% of relapsed or refractory CLL patients.
One promising strategy for CLL and other cancers is to target proteins that regulate cell death. Venclexta, developed by Abbvie and Genentech (part of the Roche group), is an oral therapy that selectively suppresses Bcl-2 — a protein highly elevated in CLL cells that helps them escape cell death.
Venclexta has shown promising results in relapsed or refractory CLL patients, including those with 17p deletion. And the addition of Rituxan to Venclexta seems to induce even better outcomes than Venclexta alone.
The combination induces clearance of minimal residual disease — small numbers of cancer cells that remain in the body after treatment and can cause relapse — which is a predictor of longer progression-free survival.
Roche and AbbVie developed a pivotal Phase 3 clinical trial named MURANO (NCT02005471) to evaluate the safety and effectiveness of the Venclexta-Rituxan combo therapy compared with a standard chemoimmunotherapy — bendamustine (Bendeka) plus Rituxan — in patients with relapsed or refractory CLL.
The ongoing open-label, randomized study enrolled 389 patients who were randomly assigned to either Venclexta for up to two years with Rituxan for the first six months or bendamustine with Rituxan for six months.
Patients were followed-up for a median of 23.8 months, and those who received the Venclexta-Rituxan combo lived significantly longer without their disease worsening compared to those who received standard chemoimmunotherapy.
At two years, 84.9% of patients in the Venclexta-Rituxan group had not experienced disease progression, compared to 36.3% of patients in the bendamustine-Rituxan group. This benefit was also observed in patients with chromosome 17 deletion — 81.5% with Venclexta-Rituxan versus 27.8% with chemoimmunotherapy.
Clinical benefits of Venclexta-Rituxan combo therapy compared with Bendamustine-Rituxan were also observed for overall survival, response rate, and clearance of minimal residual disease.
Clearance of minimal residual disease was observed in 27.3% patients in the Venclexta-Rituxan group compared with 1.5% in the Bendamustine-Rituxan group.
Researchers noted that the high rates found in the Venclexta-Rituxan group exceeded those previously achieved with other therapies, which may indicate that this combination improves disease control for a longer period even when therapy is discontinued.
The findings “suggest that greater efficacy results can be attained by replacing chemotherapy with Venclexta than by adding other targeted agents to chemoimmunotherapy,” the team wrote. Thus, Venclexta in combination with Rituxan may be an important new chemotherapy-free option for people with relapsed/refractory CLL.
No new adverse events were observed with the Venclexta-Rituxan combination therapy. Although this group showed the higher frequency of neutropenia — low levels of white blood cells — severe neutropenia with fever and severe infections were less common than in the bendamustine-Rituxan group.
The team noted that additional follow-up will be required to clarify the durability of these responses.