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AbbVie Presents New Phase 3 Data on Fixed-Duration Venetoclax-Based Combination At EHA 2026 Congress
AbbVie announced new Phase 3 data on a fixed-duration venetoclax-based combination at the European Hematology Association 2026 Congress taking place June 11-14 in Stockholm, Sweden. Final results from the Phase 3 CLL14 trial in previously untreated chronic lymphocytic leukemia (CLL), which was conducted in collaboration with the German CLL Study Group, will be featured in an oral presentation. A final analysis of the Phase 3 CLL14 trial, conducted in close collaboration with the German CLL Study Group, comparing venetoclax plus obinutuzumab to chlorambucil plus obinutuzumab in previously untreated patients with CLL and coexisting medical conditions, found that venetoclax plus obinutuzumab significantly improved progression-free survival (PFS) compared to chlorambucil plus obinutuzumab, providing a limited-duration treatment option for unfit patients with previously untreated CLL. The nine-year analysis demonstrated the long-term off-treatment efficacy and safety of the venetoclax plus obinutuzumab fixed-duration combination, with the median time to next treatment (TTNT) of 7.6 years. After a median follow-up of 9.2 years, treatment with venetoclax plus obinutuzumab resulted in superior PFS compared to the obinutuzumab plus chlorambucil group, with median PFS of 6.4 years versus 3.2 years, respectively (HR 0.50 [95% CI 0.39-0.63], pAbout the CLL14 Phase 3Trial2,5,6,7). The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial (NCT02242942 [1]), which was conducted in close collaboration with the German CLL Study Group (GCLLSG), evaluated the efficacy and safety of a combined regimen of venetoclax 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 >6 or creatinine clearance. VENCLYXTO in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy. VENCLYXTO monotherapy is indicated for the treatment of CLL: In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor. Contraindications include hypersensitivity to the active substance or to any of the excipients, concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase, and concomitant use of preparations containing St. John's wort. Tumour lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in patients with CLL when treated with venetoclax. Venetoclax poses a risk for TLS at initiation and during the dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. During post marketing surveillance, TLS, including fatal events, has been reported after a single 20 mg dose of venetoclax. The risk of TLS is a continuum based on multiple factors, including comorbidities (particularly reduced renal function), tumour burden, and splenomegaly in CLL. Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS. Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period. Serious infections, including sepsis with fatal outcome, have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections should receive prompt treatment and dose interruption or reduction, as appropriate. Live vaccines should not be administered during treatment or thereafter until B-cell recovery. CYP3A inhibitors: For patients requiring concomitant use with venetoclax, refer to the SmPC for recommendations for managing drug-drug interactions. Patients should be monitored more closely for signs of toxicities and the dose may need to be further adjusted. Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax. Additional agents that may alter venetoclax plasma concentrations include P-gp or BCRP inhibitors, CYP3A inducers (including St. John's wort), azithromycin and bile acid sequestrants. Concomitant use of these agents with venetoclax may require further dose adjustments and patients should be monitored closely for signs of toxicities. The most commonly occurring adverse reactions (=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab, ibrutinib, or rituximab were diarrhoea, neutropenia, nausea, upper respiratory tract infection, fatigue and vomiting. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection. The most frequently reported serious adverse reactions (=2%) in patients receiving venetoclax in combination with obinutuzumab, ibrutinib, or rituximab were pneumonia, febrile neutropenia, sepsis, neutropenia, anaemia, diarrhoea and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (=2%) were pneumonia and febrile neutropenia. The most commonly occurring adverse reactions (=20%) of any grade in patients treated with venetoclax in combination with acalabrutinib were infections, neutropenia, headache, bruising, diarrhoea and musculoskeletal pain. The most commonly reported Grade =3 adverse reaction (=5%) was neutropenia. The most commonly occurring adverse reactions of any grade (=20%) in patients treated with venetoclax in combination with acalabrutinib and obinutuzumab were infections, neutropenia, headache, bruising, diarrhoea, nausea and musculoskeletal pain. The most commonly reported Grade =3 adverse reactions (=5%) were neutropenia and thrombocytopenia. Discontinuations, dosage reductions and dose interruptions due to adverse reactions have occurred in both venetoclax monotherapy and in combination therapy.