AbbVie announced results from a four-year follow-up analysis of the phase 3 CLL14 trial, which showed that previously untreated patients with chronic lymphocytic leukemia (CLL) with coexisting conditions who were treated with Venclyxto /Venclexta (venetoclax) plus obinutuzumab continued to show longer progression-free survival (PFS) and higher rates of undetectable minimal residual disease (MRD) compared to patients receiving a standard of care chemoimmunotherapy regimen of obinutuzumab and chlorambucil. The data were presented for the first time today during the virtual 26th European Hematology Association (EHA) Annual Congress.
"The CLL14 trial results observed after four years of follow-up with treatment of venetoclax plus obinutuzumab show that these patients can experience long-lasting responses without disease progression, years after stopping treatment," said Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie.
After a median follow-up of more than four years (52.4 months), patients treated with the Venclyxto/Venclexta and obinutuzumab combination (n=216) continued to demonstrate longer PFS compared to patients on treatment with obinutuzumab and chlorambucil, the risk of disease progression or death was reduced by 67 percent (n=216; median not reached compared to 36.4 months; hazard ratio [HR] 0.33 [95% CI 0.25-0.45]); results are descriptive. At four years after randomization, the PFS rate for patients treated with the Venclyxto/Venclexta-based combination was 74 percent compared to 35.4 percent for patients treated with obinutuzumab and chlorambucil. The improvement in PFS was observed across all clinical and biological risk groups, including patients with TP53 mutation, 17p deletion and unmutated IGHV status.
Additionally, assessment of MRD in peripheral blood 30 months after the end of treatment showed that 26.9 percent of patients treated with the Venclyxto/Venclexta-based combination still had undetectable MRD (<10-4) compared to 3.2 percent of patients in the obinutuzumab plus chlorambucil arm. Undetectable MRD occurs when less than one CLL cell per 10,000 lymphocytes can be detected in the blood or bone marrow using sensitive analytical methods.
"CLL is considered an incurable disease and becomes more difficult to treat each time a patient experiences a relapse, so a key treatment goal is to maintain remission for as long as possible. The four- year results of the CLL14 study show that 74 percent of patients treated with fixed-duration venetoclax-obinutuzumab remain without PFS event, more than three years after treatment cessation," said Othman Al-Sawaf, M.D., lead investigator of the CLL14 study, hematologist-oncologist at the University Hospital Cologne in Germany, and study physician at the German CLL Study Group. "This highlights how durable the remissions are after 12 treatment cycles in the vast majority of patients, suggesting the venetoclax-obinutuzumab combination regimen as an effective option for patients with previously untreated CLL."
CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow. CLL is the most common form of leukemia in the Western Hemisphere, accounting for approximately one third of new leukemia diagnoses and nearly 95,000 new cases in Europe each year.
Venclyxto/Venclexta is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the US and by AbbVie outside of the US.
The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (DCLLSG), evaluated the efficacy and safety of a combined regimen of Venclyxto/Venclexta and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in previously untreated patients with CLL and coexisting medical conditions (total Cumulative Illness Rating Scale [CIRS] score >6 or creatinine clearance <70 mL/min). The therapies were administered for a fixed duration of 12 months for Venclyxto/Venclexta in combination with six cycles of obinutuzumab. The trial enrolled 432 patients, all of whom were previously untreated according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
