Venetoclax Gains FDA Approval for Previously Untreated CLL, SLL

The FDA has approved venetoclax (Venclexta) in combination with obinutuzumab (Gazyva) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), offering a chemotherapy-free regimen for patients with previously untreated disease.

The approval was supported by data coming from the CLL14 trial of 432 patients with untreated CLL with coexisting medical conditions. The randomized, multicenter trial demonstrated that the combination resulted in superior progression-free survival (PFS) compared with patients who were treated with chlorambucil plus obinutuzumab, which is commonly used as the standard of care.

Patients were treated with a 12-month regimen, and during a median follow-up of 28 months, venetoclax plus obinutuzumab reduced the risk of progression or death by 67% compared with the standard of care. Median PFS was not met in either cohort. The overall response rate was 85% among patients receiving the venetoclax combination compared with 71% among patients receiving standard of care.

For the study’s secondary end point, the researchers observed higher rates of minimal residual disease (MRD) negativity in patients treated with the venetoclax combination compared with standard of care in both bone marrow (57% vs 17%) and peripheral blood (76% vs 35%) 3 months following treatment completion.

“Patients never treated for their CLL have had to rely largely on chemotherapy as their initial treatment,” said Michael Hallek, MD, Department of Internal Medicine and Center of Integrated Oncology at the University Hospital Cologne in Germany, and lead investigator of the study, in a statement. “The approval of the Venclexta combination means that patients with previously untreated CLL now have a finite duration, chemotherapy-free treatment option that can allow them to live longer without disease progression, induce high rates of MRD negativity, and, importantly, allow them to complete their course of therapy within 12 months.”

Throughout the study, adverse events were similar to the known safety profiles of venetoclax and obinutuzumab alone. Serious adverse reactions were reported in 49% of patients receiving the venetoclax combination, most often a result of febrile neutropenia (5%) and pneumonia (5%). The most common adverse reactions of any grade included neutropenia (60%), diarrhea (28%), fatigue (21%), nausea (19%), anemia (17%), and upper respiratory urinary tract infection (17%).

In November 2018, the FDA approved venetoclax in combination with azacytidine or decitabine or low-dose cytarabine for the treatment of patients 75 years or older who are newly diagnosed with acute myeloid leukemia and have other chronic health conditions or diseases that may mean they cannot use intensive chemotherapy.