Post-Treatment Venclexta Improves Outcomes and Is Well-Tolerated in CLL

There were no major differences in outcomes for patients with previously untreated chronic lymphocytic leukemia (CLL), regardless of whether they received a fixed dose of consolidation Venclexta (venetoclax) or if their treatment was guided by their minimal residual disease status.

Consolidation therapy is given after the main line or lines of treatment to rid patients of any lingering cancer cells, known as minimal residual disease (MRD).

The data comes from the primary analysis of a phase 2 trial (HOVON 139/GiVe, NTR6043) which examined the activity and safety of 12 cycles of Venclexta consolidation after patients who were ineligible for fludarabine-based treatment was given fixed-duration Venclexta plus Gazyva (obinutuzumab). The study also aimed to see if this process could be guided by MRD status.

The open-label, multicenter, randomized trial enrolled a total of 70 patients who initially received two cycles of Gazyva given intravenously to get rid of as much cancer as possible. That was then followed by Venclexta plus Gazyva for a total of 12 cycles.

After, patients were randomly assigned and given either 12 cycles of Venclexta consolidation irrespective of MRD status or Venclexta consolidation if MRD was detected at randomization.

The main goal of the study was to see if consolidation Venclexta would lead to undetectable MRD in the bone marrow, as well as and no progressive disease three months after the end of consolidation treatment. Safety and side effects were also assessed. The analysis of the primary end point of this trial is currently ongoing.

In the study, 32 patients received fixed-dose Venclexta consolidation therapy, while 30 patients received consolidation Venclexta that was guided based on their MRD status.

At a median follow-up of 35.2 months, 16 of the 32 patients in the fixed-dose consolidation group (50%) and 16 of the 30 in the MRD-guided consolidation group (53%) met the primary endpoint of undetectable MRD in bone marrow, as well as lack of progressive disease.

Of the 32 patients in the fixed-dose Venclexta consolidation group, 22 (69%) experienced grade 2 to 4 (moderate, severe or life-threatening) side effects, compared with 11 (37%) of 30 patients in the MRD-guided consolidation group.

Overall, both methods of consolidation treatment were well-tolerated. The most common severe (grade 3 or higher) side effects were neutropenia (a decrease in a type of white blood cell), which occurred in 6% of the fixed-dose cohort and 7% in the MRD-guided group, and infection, which occurred in 6% and 3% of the fixed-dose and MRD-guided groups, respectively. There were no treatment-related deaths reported in the study.

The findings demonstrated that both maintenance treatments (fixed duration Venclexta, and MRD-guided Venclexta), were well tolerated and demonstrated high efficacy after the given cycles. MRD-guided Venclexta maintenance treatment also demonstrated slightly lower rates of side effects compared with fixed duration Venclexta.

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A version of this article was originally published on Targeted Oncology as, “Venetoclax Consolidation Is Well Tolerated in Patients with Previously Untreated CLL.”