This benefit observed with Venclexta (venetoclax) plus Rituxan (rituximab) for patients with CLL was particularly strong in patients with undetectable minimal residual disease, which may predict clinical outcome after chemoimmunotherapy.
The efficacy benefits of fixed-duration therapy with Venclexta (venetoclax) plus Rituxan (rituximab) were sustained and durable up to four years in patients with CLL who achieved undetectable minimal residual disease, or leukemic cells remaining after treatment.
It has previously been shown that minimal residual disease status at the end of chemoimmunotherapy predicts clinical outcome. Minimal residual disease has been linked to more favorable overall survival (OS) and progression-free survival (PFS), according to the four-year data from the phase 3 MURANO study published in the Journal of Clinical Oncology.
The study authors enrolled 389 patients with CLL and randomly assigned them to either Venclexta plus Rituxan (194 patients) or bendamustine plus Rituxan (195 patients). Both treatments were administered for six 28-day cycles for 2 years. After the completed cycles, patients assigned Venclexta plus Rituxan received 400 mg of Venclexta once per day for a total of 2 years.
The primary efficacy end point for this study was PFS, defined as the time from random assignment to a treatment to first occurrence of relapse, disease progression or death. Other factors that were assessed include OS, gene mutations and minimal residual disease status, which was analyzed with blood samples. Genomic complexity was analyzed in this study, although defining this in the cancer community is currently being debated. Recently, it was determined that patients CLL with five or more chromosomal aberrations, or abnormalities, was an independent predictor of adverse outcomes after chemotherapy, although this was not observed in patients with three or more aberrations. Follow-up was conducted for a median of 48 months.
At four years, more patients assigned Venclexta plus Rituxan had PFS compared with those assigned bendamustine plus Rituxan (57.3% vs. 4.6%). This was also observed for OS (85.3% vs. 66.8%). At the end of combination therapy, undetectable minimal residual disease was associated with greater PFS vs. low and high minimal residual disease positivity.
If the cancer progressed, the study authors found that the Venclexta plus Rituxan group (12 patients) had a 100% response rate with Imbruvica (ibrutinib), whereas those treated with a Venclexta-based regimen (14 patients) had a response rate of 55%.
The undetectable minimal residual disease rate after treatment with Venclexta plus Rituxan was lower in patients with genomic complexity vs. those without it. Patients with higher genomic complexity were found to have shorter PFS compared with those with lower genomic complexity.
Higher positivity rates of minimal residual disease were also observed in patients with certain mutations at the end of combination therapy (BRAF and BIRC3) and at the end of treatment (NOTCH1, TP53, BRAF and XPO1).
“The MURANO study has already shown that the safety profile of venetoclax therapy is favorable,” the study authors wrote. “The lack of long-term drug-related [serious adverse events] in the present analysis is encouraging. The fixed duration of venetoclax therapy may be advantageous over continuous therapies because it limits the period during which patients are likely to experience [adverse events].”
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