AbbVie Announces European Commission Authorization of Expanded Label for VENCLYXTO® (venetoclax) to Include Additional Combinations in Previously Untreated Chronic Lymphocytic Leukemia
- Addition of VENCLYXTO plus acalabrutinib, with or without obinutuzumab, and VENCLYXTO plus ibrutinib supported by data from Phase 3 AMPLIFY trial, Phase 3 GLOW trial and Phase 2 CAPTIVATE trial
- Fixed-duration VENCLYXTO-based combination regimens provide patients with additional CLL treatment options that may offer the potential for treatment-free intervals
NORTH CHICAGO, Ill., May 29, 2026 /PRNewswire/ -- AbbVie (NYSE:ABBV) today announced that the European Commission (EC) has authorized an expanded label for VENCLYXTO® (venetoclax) to include use in combination with acalabrutinib (with or without obinutuzumab) and use in combination with ibrutinib for the treatment of adult patients with previously untreated chronic lymphocytic leukemia (CLL). The expanded label follows the EC's inclusion of these combinations in the acalabrutinib and ibrutinib labels. These all-oral, fixed-duration combination regimens support current standards of care and offer patients and providers additional targeted oral medications for CLL in the first-line setting that include the potential for time off treatment.
The European Commission authorization extends to all European Union Member States, as well as Iceland, Norway and Liechtenstein.1
"VENCLYXTO-based combination regimens have demonstrated a favorable efficacy and safety profile in the first-line setting for chronic lymphocytic leukemia," said Svetlana Kobina, MD, PhD, vice president, global medical affairs, oncology, AbbVie. "The inclusion of additional fixed-duration, chemotherapy-free, oral VENCLYXTO combinations in the label helps address the evolving needs of patients and healthcare providers, as they consider disease management options with the potential for treatment-free intervals. AbbVie is committed to transforming standards of care for people living with cancer, and the availability of all-oral VENCLYXTO combinations expands choice and flexibility for patients and providers navigating complex treatment decisions in CLL."
VENCLYXTO in combination with acalabrutinib (with or without obinutuzumab) was supported by data from the Phase 3 AMPLIFY trial. VENCLYXTO in combination with ibrutinib was supported by data from the Phase 3 GLOW and Phase 2 CAPTIVATE trials.
"While CLL remains an incurable cancer and patients often relapse, it can be effectively managed with combination regimens, which have emerged as effective options to reduce the treatment burden for patients living with this disease," said Paolo Ghia, MD, PhD, Professor of Medical Oncology at the Università Vita-Salute San Raffaele, AMPLIFY and CAPTIVATE steering committee member and investigator. "With demonstrated durable responses in previously untreated patients and opportunity for treatment-free periods, these additional venetoclax-based combination regimens expand options for patients without the need for time-consuming infusions or continuous therapy."
CLL is one of the most common forms of leukemia in adults and is a type of cancer that can develop from cells in the bone marrow that later mature into certain white blood cells (called lymphocytes). Even with recent improvement in outcomes, patients living with CLL can still encounter difficult decisions when selecting the treatment option that best suits their individual needs.
"People living with chronic lymphocytic leukemia can face multiple challenges when it comes to managing their disease, which can take a toll on a patient's mental health and overall well-being," said Jan Rynne, interim association development lead, European CLL Association. "The possibility of time off treatment through additional combination treatment options has critical quality of life implications for patients and their families as they continue to navigate everyday life with CLL."
For a full list of side effects and information on dosage and administration, contraindications and other precautions when using VENCLYXTO in combination with acalabrutinib (with or without obinutuzumab) and use in combination with ibrutinib for the treatment of adult patients with previously untreated CLL, please refer to the Summary of Product Characteristics for further information.2
About the AMPLIFY Study
The AMPLIFY (NCT03836261) study is a randomized, global, multicenter, open-label Phase 3 trial evaluating the efficacy and safety of the fixed-duration combination regimen of VENCLYXTO and acalabrutinib, with or without obinutuzumab, compared to chemoimmunotherapy in adult patients with previously untreated CLL without del(17p) or TP53 mutation.3
Results showed that the fixed-duration combination regimen of VENCLYXTO and acalabrutinib was superior to chemoimmunotherapy. Study results showed the combination regimen reduced the risk of disease progression or death by 35% versus chemoimmunotherapy. Median progression-free survival (PFS) was not reached versus 47.6 months for chemoimmunotherapy. The triplet regimen including obinutuzumab also demonstrated clinically meaningful efficacy, with median PFS likewise not reached. The safety profiles of the combination regimens were consistent with the known safety profiles of each individual therapy alone. No new safety signals were observed in the AMPLIFY study.4
The most common adverse reactions (≥15%) of any grade in patients who received VENCLYXTO and acalabrutinib were headache (35%), diarrhea (33%), musculoskeletal pain (25%), COVID-19 (21%), fatigue (18%), bruising (17%), rash (16%), and nausea (15%). The most common laboratory abnormalities (≥15%) of any grade were neutrophils decreased (78%), glucose increased (74%), lymphocytes decreased (56%), platelets decreased (43%), hemoglobin decreased (35%), calcium decreased (30%), ALT increased (26%), urate increased (25%), LDH increased (24%), potassium increased (22%), AST increased (22%), ALP increased (20%), glucose decreased (20%), creatinine increased (19%), and sodium increased (15%). Grade 4 laboratory abnormalities in >15% of patients included absolute neutrophil count decreased (15%).
Serious adverse reactions occurred in 25% of patients receiving VENCLYXTO and acalabrutinib. The most common serious adverse reactions (≥2%) were COVID-19, including COVID-19 pneumonia (9%), second primary malignancies (2.7%) and neutropenia (2.1%). Fatal adverse events occurred in 3.4% of patients. The most common fatal adverse events included COVID-19 and COVID-19 pneumonia.
About the GLOW Study
The GLOW (NCT03462719) study is a randomized, open-label Phase 3 trial comparing progression-free survival in patients treated with the fixed-duration combination regimen of VENCLYXTO and ibrutinib or chlorambucil plus obinutuzumab in adult patients with previously untreated CLL.5
Results from the 64-month follow-up to the GLOW study showed that the fixed-duration combination regimen of VENCLYXTO and ibrutinib demonstrated a clinically meaningful improvement in PFS and overall survival (OS) compared to chlorambucil plus obinutuzumab for older patients and/or those with comorbidities with previously untreated CLL. At 64 months of follow-up, VENCLYXTO and ibrutinib reduced the risk of disease progression or death by 73% compared to chlorambucil plus obinutuzumab. For OS, the regimen reduced the risk of death by 54%. Study results showed a median PFS of 65 months in the venetoclax plus ibrutinib arm versus 23 months in the chlorambucil plus obinutuzumab arm.6
The safety profile of VENCLYXTO and ibrutinib was generally consistent with the safety profile of the single agents and tolerability profiles were consistent with CLL treatment in the enrolled patient population. Most common grade ≥3 treatment-emergent adverse events (AEs) were neutropenia (34.9%), infections (17%), and diarrhea (10.4%) for VENCLYXTO and ibrutinib; neutropenia (49.5%), infections (11.4%), and thrombocytopenia (20%) for chlorambucil plus obinutuzumab. Deaths during treatment occurred in seven patients on VENCLYXTO and ibrutinib and two patients on chlorambucil plus obinutuzumab.
The VENCLYXTO and ibrutinib regimen was well-tolerated and no adverse events of tumor lysis syndrome (TLS) were observed in the venetoclax plus ibrutinib arm, compared to 6 cases in the chlorambucil with obinutuzumab arm. At 64-months follow-up, the time patients spent without significant toxicity or disease progression was significantly longer for VENCLYXTO and ibrutinib versus chlorambucil plus obinutuzumab (52 months vs 31 months). Treatment-emergent adverse event-free PFS (TEAE-free PFS) analysis showed that while patients receiving 15 months of VENCLYXTO and ibrutinib spent slightly more time in the grade 3/4 toxicity state versus patients receiving 6 months of chlorambucil plus obinutuzumab (2 months vs 1 month), patients who received VENCLYXTO and ibrutinib spent substantially more time in TEAE-free PFS (50 months vs 30 months), indicating longer disease control without significant toxicity.
About the CAPTIVATE Study
The CAPTIVATE (NCT02910583) study is a multicenter, two-cohort Phase 2 trial assessing both minimal residual disease (MRD)-guided discontinuation and fixed duration therapy with the combination of VENCLYXTO plus ibrutinib in adult patients with previously untreated CLL or small lymphocytic lymphoma (SLL).7
Results showed that the fixed-duration combination regimen of VENCLYXTO plus ibrutinib demonstrated 5.5-year PFS and overall survival (OS) rates of 66% and 97%, respectively; 73% of CLL patients remained treatment-free 5.5 years after 15 months of VENCLYXTO plus ibrutinib therapy.8
The most common treatment-emergent AEs in patients who received VENCLYXTO plus ibrutinib were diarrhea (62%), nausea (43%), neutropenia (42%) and arthralgia (33%); AEs were primarily grade 1 or 2 in severity. The most common grade 3/4 AEs were neutropenia (33%), hypertension (6%) and neutrophil count decreased (5%). One fatal AE (sudden death) occurred during ibrutinib lead-in. Serious AEs occurred in 36 patients (23%).
About VENCLYXTO
VENCLYXTO® (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.
VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.
VENCLYXTO (venetoclax) EU Indication and Summary of Important Safety Information
Venclyxto is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL):
- in combination with acalabrutinib with or without obinutuzumab
- in combination with obinutuzumab
- in combination with ibrutinib
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
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. Concomitant use of preparations containing St. John's wort.
Special Warnings & Precautions for Use
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.
Drug Interactions
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.
Adverse Reactions
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.
Special Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Venetoclax should be administered to patients with severe renal impairment (CrCl ≥15 ml/min and <30 ml/min) or end-stage renal disease (ESRD) requiring dialysis (CrCL <15ml/min) only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.
For patients with severe hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended. These patients should be monitored more closely for signs of toxicity.
Women should avoid becoming pregnant while taking venetoclax and for at least 30 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking venetoclax and for 30 days after stopping treatment. Venetoclax may harm the foetus when administered to a pregnant woman. Breast-feeding should be discontinued during treatment with venetoclax.
This is not a complete summary of all safety information. Refer to the prescribing information of each of the medicinal products used in combination with venetoclax for additional information for management of toxicities. See VENCLYXTO (venetoclax) SmPC at www.ema.europa.eu. Globally, prescribing information varies. Refer to the individual country product label for complete information.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas including immunology, oncology, neuroscience and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter) and YouTube.
About AbbVie in Oncology
AbbVie is committed to elevating standards of care and bringing transformative therapies to patients worldwide living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities and biology interventions, including small molecule therapeutics, antibody-drug conjugates (ADCs), immuno-oncology-based therapeutics, multispecific antibody and novel CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.
Today, our expansive oncology portfolio comprises approved and investigational treatments for a wide range of blood cancers and solid tumors. We are evaluating more than 35 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry, the impact of global macroeconomic factors, such as economic downturns or uncertainty, international conflict, trade disputes and tariffs, and other uncertainties and risks associated with global business operations. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2025 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
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1European Medicines Agency. Conditional marketing authorisation. European Medicines Agency website. Accessed May 2026. Available at: https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/conditional-marketing-authorisation
2VENCLYXTO Summary of Product Characteristics (SmPC).
3ClinicalTrials.gov. Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL (AMPLIFY). Available at: https://clinicaltrials.gov/study/NCT03836261. Accessed May 2026.
4Brown JR, Seymour JF, Jurczak W, et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025;392(8):748-762. https://www.nejm.org/doi/abs/10.1056/NEJMoa2409804
5ClinicalTrials.gov. A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (GLOW). Available at: https://clinicaltrials.gov/study/NCT03462719. Accessed May 2026.
6Niemann CU, Munir T, Owen C, et al. First-Line Ibrutinib Plus Venetoclax Vs Chlorambucil Plus Obinutuzumab in Elderly or Comorbid Patients (Pts) with Chronic Lymphocytic Leukemia (CLL): Glow Study 64-Month Follow-up (FU) and Adverse Event (AE)-Free Progression-Free Survival (PFS) Analysis. Blood. 2024;144 (Supplement 1):1871. https://doi.org/10.1182/blood-2024-203269
7ClinicalTrials.gov. Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL) (Captivate). Available at: https://clinicaltrials.gov/study/NCT02910583. Accessed May 2026.
8Allen J, Siddiqi T, Kipps TJ, et al. Treatment Outcomes After Undetectable MRD With First-Line Ibrutinib (Ibr) Plus Venetoclax (Ven): Fixed Duration Treatment (Placebo) Versus Continued Ibr With Up to 5 Years Median Follow-up in the CAPTIVATE Study. 2022 American Society of Hematology (ASH) Annual Meeting. December 11, 2022.
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