Long-Term Data Support Use of Venclexta-Gazyva in Patients With Previously Untreated Chronic Lymphocytic Leukemia

Results from a randomized phase 3 study presented at the 2020 ASCO Virtual Scientific Program show that the combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) elicited superior efficacy, which was maintained in long-term follow up, compared to Leukeran (chlorambucil) and Gazyva in patients with previously untreated chronic lymphocytic leukemia.

“The superior efficacy of venetoclax-obinutuzumab has been observed and maintained in the current follow up,” Dr. Othman Al-Sawaf, of University Hospital of Cologne in Germany, said during a pre-recording presentation. “And, of note, these benefits were observed across all known risk categories, indicating that this regimen is a viable option for patients with previously untreated CLL.”

Within the CLL14 trial, 432 patients were randomized to receive six cycles of Gazyva with either 12 cycles of Venclexta (216) or 12 cycles of Leukeran (216). Investigator-assessed progression free survival (PFS) served as the primary outcome of the study. Additional endpoints included response rates, overall survival and minimal residual disease, which indicates that disease can still be detected once treatment has stopped.

Rates of minimal residual disease were measured every six months up to five years after the last patient was enrolled.

Although all patients are no longer on study treatment, follow-up is still ongoing. Currently, following a median observation period of 39.5 months, patients who received Venclexta and Gazyva achieved a three-year PFS rate of 81.9% compared to 49.5% in those who received Leukeran and Gazyva.

Patients who received the Venclexta and Gazyva combination have not yet reached a median PFS, while patients in the other arm reached a median PFS of 35.6 months.

Al-Sawaf noted that the benefits were observed in patients across all risk groups, including patients with mutated/deleted TP53 and unmutated immunoglobulin heavy chain variable region gene (IGHV) status. The researchers did not observe a difference in overall survival between the two treatment arms in the study. And, a median overall survival was not reached in either group.

Interestingly, according to Al-Sawaf, the researchers also observed a benefit in those with a mutated IGHV status who received Venclexta and Gazyva.

“This is particularly interesting, as in the earlier follow up, no PFS difference had been observed between both treatment arms in patients with mutated IGHV status,” he said. “However, now with the longer follow up, it becomes clear that venetoclax-obinutuzumab also yields higher efficacy for patients with mutated IGHV status, compared to chemo monotherapy.”

Almost half (47.2%) of the patients who received the Venclexta and Gazyva combination had undetectable minimal residual disease after 18 months following treatment completion compared to 7.4% in the other treatment arm.

Patients from both the Venclexta and Gazyva (17%), and Leukeran and Gazyva (10.3%) treatment arms developed secondary primary malignancies. However, no new side effects were observed during follow-up.

“A landmark PFS analysis … was performed based on different groups of minimal residual disease, and you can appreciate that patients with undetectable MRD levels, or the lowest MRD levels, continuously show the longest progression free survival,” Al-Sawaf said. “And, of note, also patients with partial response and undetectable minimal residual disease had the same PFS as patients with complete response and undetectable minimal residual disease, indicating that irrespective of clinical response, the PFS outcome is excellent when undetectable minimal residual disease levels are achieved.”