Venclyxto/Venclexta continues to show sustained progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients

The results were presented during oral sessions at the European Hematology Association (EHA) Annual Congress in Frankfurt, Germany.

"Results from the CLL14 and MURANO studies demonstrate the long-term benefits of fixed-duration venetoclax combinations for patients living with CLL," said Mariana Cota Stirner, M.D., Ph.D., vice president, hematology, AbbVie. "These results underscore our commitment to transform how blood cancers are treated today and show that venetoclax can give patients lasting results with time off treatment."

CLL14 Long-Term Analysis: New six-year follow-up results from the Phase III CLL14 study showcase updated outcomes in previously untreated patients with CLL and co-existing conditions. Patients treated with fixed-duration venetoclax plus obinutuzumab continued to experience improved PFS (95% Confidence Interval (CI) 0.31-0.52; Hazard Ratio (HR) 0.40) and higher rates of undetectable minimal residual disease (uMRD) when treated with fixed-duration venetoclax plus obinutuzumab compared to those who received chlorambucil plus obinutuzumab (53.1% vs 21.7%, respectively). The data also showed significantly improved rates of time to next treatment (TTNT) with venetoclax plus obinutuzumab at 65.2 percent (95% CI 0.33-0.58; HR 0.44) compared to chlorambucil plus obinutuzumab at 37.1 percent. The observed differences in PFS and TTNT benefits between venetoclax-based treatment and chemoimmunotherapy were maintained across all risk groups, including patients with high-risk molecular features of CLL. No new safety signals were observed in this six-year analysis. The most frequently occurring Grade 3 ( greater than 2%) adverse events (AEs) in patients receiving the venetoclax-based combination were neutropenia, thrombocytopenia, infusion-related reaction (during treatment), anemia, febrile neutropenia, pneumonia and leukopenia.

"The latest findings show that patients can experience long-term disease control, five years after stopping treatment," said Othman Al-Sawaf, M.D., investigator in the CLL14 study, hematologist-oncologist at the University Hospital Cologne in Germany, and study physician at the German CLL Study Group. "These results confirm the treatment benefits of fixed-duration venetoclax and obinutuzumab for previously untreated CLL patients with co-existing conditions."

MURANO Long-Term Analysis; Final data from the Phase III MURANO trial showcase that R/R CLL patients treated with two-year fixed-duration venetoclax plus rituximab sustained significantly longer median PFS at 54.7 months (95% CI 52.3, 59.9), the study's primary endpoint, compared to 17.0 months (95% CI 15.5, 21.7; HR 0.23) with bendamustine plus rituximab after 7 years of median follow-up. Seven-year OS rates were 69.6 percent (95% CI 62.8, 76.5) for patients treated with the venetoclax-based combination versus 51 percent (95% CI 43.3, 58.7) for study participants who received bendamustine-based combination (HR 0.53). Furthermore, most of the patients treated with the full two-year venetoclax-based combination achieved uMRD (70.3%) at the end of their treatment course, and those patients were shown to have improved PFS and OS compared to patients with detectable MRD (29.7%).

The safety profile of the venetoclax-rituximab combination is consistent with the known safety profile of each individual therapy alone. No new serious safety issues were observed in the MURANO updated analysis. The most common adverse reactions (ARs) ( greater than 20%) of any grade were neutropenia, diarrhea, upper respiratory tract infection, fatigue, and nausea.

About the CLL14 Phase III Trial; The prospective, multicenter, open-label, randomized Phase III CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (GCLLSG), 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 co-existing medical conditions (total Cumulative Illness Rating Scale [CIRS] score greater tha 6 or creatinine clearance <70 ml min). the therapies were administered for a fixed-duration of 12 months for venclyxyo venclyxta 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. efficacy was based on pfs, as assessed by an independent review committee.key secondary endpoints were rates of mrd in peripheral blood and bone marrow, overall and complete response rates, mrd in complete response in peripheral blood and bone marrow, and os. in patients with cll receiving venetoclax combination therapy with obinutuzumab, the most frequently occurring grade 3 aes ( greater than 2%) were neutropenia (51.9%), thrombocytopenia (14.2%), infusion-related reaction (9.0%), anemia (7.5%), febrile neutropenia (4.2%), pneumonia (3.8%) and leukopenia (2.4%). serious ars were most often due to febrile neutropenia and pneumonia (5% each). the most common ars ( greater than 20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). fatal ars that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2 percent (4 212) of patients, most often from infection.

About the MURANO Phase III Trial: A total of 389 patients with R/R CLL who had received at least one prior therapy were enrolled in the international, multicenter, open-label, randomized Phase III MURANO trial. The trial was designed to evaluate the efficacy and safety of Venclyxto/Venclexta and rituximab (n=194) compared with bendamustine and rituximab (n=195). The median age of patients in the trial was 65 years (range: 22 to 85). The trial met its primary efficacy endpoint of investigator (INV)-assessed PFS. At the time of the primary analysis, median PFS with Venclyxto/Venclexta and rituximab was not reached compared with 17.0 months for bendamustine and rituximab (HR: 0.17; 95% CI: 0.11- 0.25; p<0.0001). in the primary efficacy analysis, the median follow-up for pfs was 23.8 months (range: 0 to 37.4). additional efficacy endpoints included independent review committee (irc)-assessed pfs, inv- and irc-assessed overall response rate (defined as complete response + complete response with incomplete marrow recovery + partial response + nodular partial response), os and rates of mrd-negativity.

In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (AR; greater than 5%) was pneumonia (9%). The most common ARs ( greater than 20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fatal ARs that occurred in the absence of disease progression and within 30 days of the last venetoclax treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.