Venclexta Combination Receives Full FDA Approval for CLL, With or Without 17p deletion

The Food and Drug Administration (FDA) approved Venclexta (venetoclax) in combination with Rituxan (rituximab) for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without the genetic mutation 17p deletion, who have received at least one prior therapy.

"Venclexta now gives indicated patients a new opportunity to significantly reduce the risk of their disease progressing, compared to a current standard of care. This combination provides previously treated CLL or SLL patients with a chemotherapy-free, fixed duration treatment allowing patients the ability to stop treatment after approximately two years," Michael Severino, M.D., executive vice president of research and development, and chief scientific officer of AbbVie, said in a press release.

The agency based its decision on data from the randomized, multicenter, open-label phase 3 MURANO trial — designed to evaluate Venclexta plus Rituxan compared with a standard of care chemoimmunotherapy regimen - bendamustine plus Rituxan - in 389 patients with CLL who had received at least one prior line of therapy.

Patients in the Venclexta arm completed a five-week “ramp-up” schedule before receiving 400 mg of Venclexta once daily for 24 months. Rituxan, which was administered after the “ramp-up” schedule, was given for six 28-day cycles (375 mg/m2 intravenously on cycle one day one and 500 mg/m2 intravenously on day one of cycles two through six).

Overall, 194 patients received the Venclexta regimen and 195 were given chemotherapy plus Rituxan.

After approximately 23 months of follow-up, the median progression-free survival was not reached in the Venclexta arm but was 18.1 months with the chemotherapy regimen.

However, patients who received Venclexta plus Rituxan experienced superior overall response rates compared with those who were treated with bendamustine and Rituxan (92 percent vs. 72 percent).

"The approval of the combination of Venclexta plus rituximab for patients with relapsed/refractory CLL or SLL validates the results seen in the phase 3 trial, including the significant improvement in progression-free survival over a standard of care comparator arm," lead investigator John Seymour, Ph.D., MBBS, director of cancer medicine at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia, said in the release. "Progression-free survival is considered a gold standard for demonstrating clinical benefit in oncology."

Grade 3/4 side effects were more common with Venclexta compared with bendamustine (82 percent vs. 70.2 percent, respectively), with neutropenia as the most common grade 3/4 side effect in both groups (57.7 percent vs. 38.8 percent, respectively). Additional grade 3/4 side effects included febrile neutropenia (3.6 percent vs. 9.6 percent, respectively) and infections or infestations (17.5 percent vs 21.8 percent, respectively).

Ten deaths (5.2 percent) occurred in the Vencelxta arm vs. 11 in the bendamustine arm (5.9 percent).

The FDA previously granted an accelerated approval to the BCL-2 inhibitor, manufactured by AbbVie and Genentech, in combination with Rituxan for patients with CLL/SLL harboring a 17p deletion following at least one prior therapy.