Venclexta Plus Gazyva Reduces Disease Progression by 65% in Patients with CLL

The addition of Venclexta (venetoclax) to Gazyva (obinutuzumab) induced prolonged progression-free survival — or the time from treatment to disease worsening – among patients with previously untreated chronic lymphocytic leukemia (CLL), according to results from the pivotal phase III CLL14 study.

Moreover, the combination regimen reduced the risk for disease worsening or death by 65% compared with Gazyva plus chlorambucil, and nearly nine of 10 patients (88.2%) in the Venclexta arm remained progression free at two years, compared with 64.1% in the Gazyva plus chlorambucil arm.

“The results of our phase 3 CLL14 trial, reported today at (the 2019 ASCO Annual Meeting) and in the New England Journal of Medicine, represent a major advance in improving outcomes in chronic lymphocytic leukemia,” Dr. Sandra Horning, chief medical officer and head of global product development, Roche, said in a press release. “We are pleased this fixed-duration, chemotherapy-free regimen of Venclexta plus Gazyva was approved by the FDA (on May 15, 2019) and look forward to providing an important treatment option to even more adults with the most common form of adult leukemia.”

In the multinational, open-label, phase 3 trial, the researchers evaluated a fixed-duration treatment using Venclexta plus Gazyva in 432 patients with previously untreated CLL and coexisting conditions, which included reduced kidney function or comorbidities assessed by a standard scale: the Cumulative Illness Rating Scale score ranges from 0 to 56, with higher scores indicating more impaired function of organ systems.

Investigator-assessed progression-free survival served as the primary endpoint, and secondary endpoints included progression-free survival assessed by independent review committee, minimal residual disease status, overall response rate, complete response with at least partial blood count recovery, overall survival, duration of response, event-free survival, time to next CLL treatment and safety.

Patients were a median age of 72 and had a median Cumulative Illness Rating Scale score of 8 and median creatinine clearance of 66.4 ml per minute.

After a median follow-up of 28.1 months, 30 patients experienced disease progression or death in the Venclexta/Gazyva group and 77 in the Gazyva/chlorambucil group. Meanwhile, the percentage of patients with progression-free survival at two years was significantly higher with the addition of Venclexta to Gazyva, compared with chlorambucil. Median progression-free survival reported by investigators was not yet reached in either arm; however, independent review committee assessment of progression-free survival was consistent.

The Venclexta/Gazyva group also demonstrated clinical benefit across secondary endpoints, including ORR (84.7% vs. 71.3%); complete response including incomplete marrow recovery (49.5% vs. 23.1%); and higher rates of minimal residual disease-negativity (56.9% vs. 17.1%) and peripheral blood (75.5% vs. 35.2%) three months after treatment.

The safety profile of both treatments showed no new safety signals or higher incidences of known toxic effects. The most common grade 3 or higher side effects in the Venclexta/Gazyva group group and Gazyva/chlorambucil group were neutropenia (52.8% vs 48.1%, respectively) and infections (17.5% vs 15.0%). All-cause mortality occurred in 9.3% and 7.9% of patients, respectively; however, these differences were not significant.

“Fixed-duration, targeted treatment with venetoclax—obinutuzumab was effective in previously untreated patients with CLL and coexisting conditions and resulted in a significantly higher percentage of patients with progression-free survival than standard treatment with chlorambucil–obinutuzumab,” the researchers concluded. “Longer follow-up is necessary to assess the durability of the responses.”

This article was adapted from and originally appeared on OncLive as "Chemo-Free Combo Significantly Improves PFS in Previously Untreated CLL."