New Data Shows AbbVie's VENCLYXTO®/VENCLEXTA® Fixed Duration Combination Demonstrates Sustained Progression-Free Survival in Chronic Lymphocytic Leukemia Patients after Three Years off Treatment
AbbVie (NYSE: ABBV) reported results from a four-year follow-up of the Phase 3 CLL14 trial, demonstrating that patients with chronic lymphocytic leukemia (CLL) treated with the VENCLYXTO/VENCLEXTA and obinutuzumab combination had significantly improved progression-free survival (PFS) and higher undetectable minimal residual disease (MRD) rates compared to those receiving standard chemoimmunotherapy. The PFS rate at four years for the combination was 74%, while it was 35.4% for the standard treatment. No new safety concerns were reported, affirming the treatment’s effectiveness.
- PFS rate at four years for VENCLYXTO/VENCLEXTA plus obinutuzumab is 74% vs. 35.4% for standard treatment.
- 67% reduction in risk of disease progression or death (HR 0.33).
- 26.9% with undetectable MRD compared to 3.2% in the control group.
- No new safety signals during the four-year follow-up.
- None.
NORTH CHICAGO, Ill., June 11, 2021 /PRNewswire/ -- AbbVie (NYSE: ABBV) today 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 (abstract #S146).
"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 [
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.1 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.2
No new safety signals were observed in the four-year follow-up analysis.1 The most frequently occurring serious adverse reactions (>=
"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.4,5,6
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 U.S. and by AbbVie outside of the U.S.
About the CLL14 Phase 3 Trial3,7,8
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. 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 overall survival.
The four-year, follow-up analysis showed an OS rate of
In patients with CLL receiving combination therapy with obinutuzumab, serious adverse reactions (ARs) were most often due to febrile neutropenia and pneumonia (5 percent each). The most common ARs (≥20 percent) of any grade were neutropenia (60 percent), diarrhea (28 percent), and fatigue (21 percent). 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 VENCLYXTO® (venetoclax)
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.
Indication and Important VENCLYXTO (venetoclax) EU Safety Information3
Indications
Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
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.
Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.
Contraindications
Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumour lysis syndrome (TLS). Concomitant use of preparations containing St. John's wort as Venclyxto efficacy may be reduced.
Special Warnings & Precautions for Use
Tumour Lysis syndrome, including fatal events, has occurred in patients when treated with Venclyxto. For CLL and AML, please refer to the indication-specific recommendations for prevention of TLS in the Venclyxto summary of product characteristic (SmPC).
Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS. The risk of TLS is a continuum based on multiple factors, including comorbidities. Venclyxto 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.
Neutropenia (grade 3 or 4) has been reported. Complete blood counts should be monitored throughout the treatment period.
In patients with AML, neutropenia (grade 3 or 4) is common before starting treatment. The neutrophil counts can worsen with Venetoclax in combination with a hypomethylating agent. Neutropenia can recur with subsequent cycles of therapy. Dose modification and interruptions for cytopenias are dependent on remission status.
For CLL and AML, please refer to the indication-specific recommendations for dose modifications for toxicities in the Venclyxto SmPC.
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 including antimicrobials and dose interruption or reduction as appropriate.
Live vaccines should not be administered during treatment or thereafter until B-cell recovery.
Drug Interactions
In CLL and AML CYP3A inhibitors may increase Venclyxto plasma concentrations.
In CLL, at initiation and dose-titration phase, Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, please refer to the recommendations for dose modifications in the Venclyxto SmPC.
In AML, please refer to the AML-specific recommendation for dose modifications for potential interactions with CYP3A inhibitors, in the VENCLYXTO SmPC.
Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.
CYP3A4 inducers may decrease Venclyxto plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.
Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.
Adverse Reactions
CLL
The most commonly occurring adverse reactions (>=
The most frequently occurring serious adverse reactions (>=
Discontinuations due to adverse reactions occurred in
Dosage reductions due to adverse reactions occurred in
AML
The most commonly occurring adverse reactions (>=
The most frequently reported serious adverse reactions (≥
Discontinuations due to adverse reactions occurred in
Dosage reductions due to adverse reactions occurred in
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. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined.
For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least
Venclyxto may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.
This is not a complete summary of all safety information. 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 in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 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.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines 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: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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, among others, 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 indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2020 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
1 Al-Sawaf O, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 4-year follow-up analysis of the randomized CLL14 study. Presented at the European Hematology Association Annual Meeting; June 11, 2021. | ||
2 Hallek M, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;131(25):2745-2760. | ||
3 Summary of Product Characteristics for VENCLYXTO (venetoclax). Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG. | ||
4 International Agency for Research on Cancer. World Health Organization. Europe Globocan 2018. https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf. Accessed February 2020. | ||
5 NCI Dictionaries. NCI Dictionary of Terms. Chronic Lymphocytic Leukemia. https://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed January 2020. | ||
6 World Health Organization. 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. http://www.who.int/selection_medicines/committees/expert/20/applications/CLL.pdf. Accessed January 2020. | ||
7 VENCLEXTA (venetoclax) [Package Insert]. North Chicago, Ill.: AbbVie Inc. | ||
8 Fischer K, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236. | ||
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FAQ
What were the results of AbbVie's CLL14 trial presented on June 11, 2021?
How does the VENCLYXTO/VENCLEXTA combination compare to standard treatment for CLL?
What is the significance of undetectable MRD in CLL patients treated with AbbVie's therapy?
Were there any new safety concerns in the CLL14 trial findings?
