Venclexta-Gazyva Combo Creates More Long-Term Treatment Options for Patients with CLL

Treatment with the combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) in patients with chronic lymphocytic leukemia (CLL) demonstrated a superior efficacy and increased progression-free survival compared to the chemotherapy chlorambucil plus Gazyva, according to Dr. Othman Al-Sawaf.

Al-Sawaf, a physician at the University Hospital of Cologne in Germany, recently presented results of the CLL14 trial at the 2020 American Society of Clinical Oncology (ASCO) Virtual meeting. The goal of the trial was to assess the safety and efficacy of the two combinations in 432 randomized patients with previously untreated CLL.

The main finding was that at 24 months, estimated progression-free survival (PFS) was 88.2% for Venclexta-Gazyva compared to 64.2% in the chemotherapy-Gazyva arm. Moreover, Venclexta-Gazyva had a lower incidence of high-level side effects with 80% of patients completing the treatment. However, there was no significant difference in overall survival.

“We wanted to see whether particularly elderly patients and those who are not fit enough to receive intensive chemoimmunotherapy and were traditionally treated with mild chemoimmunotherapy, such as chlorambucil/obinutuzumab, which was the standard-of-care arm chosen for this trial,” Al-Sawaf said in an interview with CURE®’s sister publication, OncLive®. “We wanted to see whether we can challenge that with a more effective therapy that is, at the same time, at least as tolerable as a mild chemoimmunotherapy.”

The trial’s follow-up analysis occurred three years after treatment had ended, which according to Al-Sawaf, demonstrated a significant deep response. The PFS benefit was also sustained among all CLL risk groups in the trial including patients with mutations in the TP53 gene, a gene that helps to stop the growth of tumors, and patients with an unmutated IGHV status. However, for patients with mutated IGHV status, the immunoglobulin heavy chain variable region gene that is a prognostic factor in CLL, had a higher benefit from Venclexta-Gazyva which differed in the initial analysis.

“We saw that patients who were treated with chemoimmunotherapy had a similar favorable PFS when they had a mutated IGVH status; this is in line with what we see with all sorts of chemoimmunotherapy,” explained Al-Sawaf. “With this follow-up analysis, we do see now that venetoclax/obinutuzumab even improves outcomes in this particular group of patients. Thereby, all patients in all risk groups benefit from venetoclax/obinutuzumab.”

Minimal residual disease, or the amount of cancer cells that linger in a patient during and after treatment/remission, is under further observation as about half of patients have a detectable MRD compared to 7% of the patients from the chemotherapy arm. However, according Al-Sawaf, this has not led to real disease progression in the patients with detectable MRD where the vast majority of patients will not need treatment for several years.

“What we can do now is to discuss with our patients their individual preferences. Some patients say that they do not want to get any infusions and they do not want to have regular visits with a hematologist—or at the very least, less frequent [visits],” he concluded regarding the clinical significance of the treatment. “For those patients, continuous treatments might be a very feasible option, so setting them on a continuous (Bruton’s tyrosine kinase) inhibitor might be of particular value. On the other hand, some patients just want to know that they received the treatment for one year and that they can stop treatments; that seems to be much more favorable for them than a continuous treatment.”