Data from two studies continue to show the long-term efficacy and safety of fixed-duration venetoclax combination regimens across different lines of therapy in CLL Six-year median follow-up from the Phase 3 CLL14 study shows continued PFS after treatment with venetoclax plus obinutuzumab compared to treatment with chlorambucil plus obinutuzumab in previously untreated patients with CLL and co-existing conditions NORTH CHICAGO, Ill., June 9, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new findings demonstrating sustained long-term safety and efficacy of VENCLYXTO®/ VENCLEXTA® (venetoclax)-based combination therapies in patients with previously untreated CLL with co-existing conditions, as well as R/R CLL. The results are being 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." New six-year follow-up results from the Phase 3 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.1 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. "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." Results will also be featured at EHA's Press Briefing.
MURANO Long-Term Analysis
Final data from the Phase 3 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.2 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).2 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%). About the CLL14 Phase 3 Trial1,3
The prospective, multicenter, open-label, randomized Phase 3 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 >6 or creatinine clearance 2,4 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 3 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). 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. 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 AMLAML, 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 AMLAML, 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.
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 AMLAML, please refer to the AMLAML-specific recommendation for dose modifications for potential interactions with CYP3A inhibitors, in the VENCLYXTO SmPC. Avoid concomitant use of P-gp and BCRP inhibitorsBCRP 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. Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions. Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14, in 15% of patients treated with the combination of venetoclax and rituximab in Murano, and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia. The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in combination with azacitidine or decitabine in the VIALE-A and M14-358, respectively, were thrombocytopenia, neutropenia, febrile neutropenia, nausea, diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and decreased appetite, haemorrhage, dizziness/syncope, hypotension, headache, abdominal pain, and anaemia. Discontinuations due to adverse reactions occurred in 24% of patients treated with venetoclax in combination with azacitidine in the VIALE-A study, and 26% of patients treated with venetoclax in combination with decitabine in the M14-358 study, respectively. Dosage reductions due to adverse reactions occurred in 2% of patients in VIALE-A, and in 6% of patients in M14-358. Venetoclax dose interruptions due to adverse reactions occurred in 72% and 65% of patients, respectively. The most common adverse reaction that led to dose interruption (>10%) of Venetoclax in VIALE-A, were febrile neutropenia, neutropenia, pneumonia, and thrombocytopenia. The most common adverse reactions that led to dose interruption (≥5%) of venetoclax in M14-358 were febrile neutropenia, neutropenia/neutrophil count decreased, pneumonia, platelet count decreased, and white blood cell count decreased. Patients with reduced renal function (CrCl
. Globally, prescribing information varies; refer to the individual country product label for complete information.
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 and our Blood Cancer Press Kit page. 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 and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn. AbbVie 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, 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 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. 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. Al-Sawaf O, et al. Venetoclax-Obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. Abstract No. S145. Presented orally at European Hematology Association 2023 Hybrid Congress, Frankfurt, Germany, June 8-11. Fischer K, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380:2225-2236.