On May 31, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported it will present data from clinical trials across multiple blood cancers evaluating venetoclax, a first-in-class oral B-cell lymphoma-2 (BCL-2) inhibitor, as monotherapy and in combination with other therapies at the 23rd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, June 14-17, in Stockholm, Sweden (Press release, AbbVie, MAY 31, 2018, View Source [SID1234526983]). A total of 11 abstracts will be presented, including results of venetoclax in chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), multiple myeloma (MM) and acute lymphoblastic leukemia (ALL). Venetoclax 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.
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Studies of venetoclax in CLL and AML have been chosen for oral presentations, including an undetectable minimal residual disease (uMRD) sub-analysis from the pivotal Phase 3 MURANO study of venetoclax in combination with rituximab in patients with relapsed/refractory (R/R) CLL. Minimal residual disease is an objective measure of disease defined by the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.1 Prospective clinical trials have suggested that achieving undetectable minimal residual disease, also known as MRD negativity (MRD-), may have a prognostic impact on clinical outcomes.2
"The breadth of venetoclax studies being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, across four blood cancers, is an indicator of the utility, versatility and potential to advance care for patients living with blood cancer around the world,"3 said Neil Gallagher, M.D., Ph.D., head of oncology clinical development, AbbVie. "As a company, we are committed to exploring additional therapeutic applications for venetoclax in our efforts to address major unmet medical needs, and develop novel treatments that work against key pathways of disease progression."
Key presentations featuring venetoclax include:
Venetoclax in CLL
High, Durable Minimal Residual Disease Negativity (MRD-) with Venetoclax + Rituximab (VenR) in Relapsed/Refractory (R/R) CLL: MRD Kinetics from Phase 3 MURANO Study. Hillmen et al.; Abstract S805; Oral Presentation; Saturday, June 16, 2018, 11:45 a.m.-12:00 p.m. CEST
Durability Response to Venetoclax (VEN) in Patients with CLL Who Are Relapsed/Refractory after Ibrutinib and/or Idelalisib. Byrd et al.; Abstract PF340; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
Impact of TP53 Mutated Clone Size on Outcome of Relapsed/Refractory (R/R) CLL Patients Treated with Venetoclax plus Rituximab within the Phase 3 MURANO Study. Kater et al.; Abstract PF344; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
Venetoclax Improves Quality of Life for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Cochrane et al.; Abstract PS1438; Poster Session; Saturday, June 16, 2018; 5:30-7:00 p.m. CEST
Indirect Treatment Comparison of Venetoclax Plus Rituximab with B-Cell Receptor Inhibitors in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. Mato et al.; Abstract PF358; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
Management, Adverse Events, and Outcomes of 282 CLL Patients Treated with Venetoclax in the Real World. Nabhan et al.; Abstract PF342; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
Venetoclax in AML
Durable Response with Venetoclax in Combination with Decitabine or Azacitadine in Elderly Patients with Acute Myeloid Leukemia (AML). DiNardo et al.; Abstract S1563; Oral Presentation; Sunday, June 17, 2018; 8:45-9:00 a.m. CEST
Cytogenic and Molecular Drivers of Outcome with Venetoclax-Based Combination Therapies in Treatment-Naïve Elderly Patients with AML. Strickland et al.; Abstract PS982; Poster Session; Saturday, June 16, 2018; 5:30-7:00 p.m. CEST
Venetoclax in MM
Phase 2 Study of Venetoclax Plus Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. Costa et al.; Abstract PF558; Poster Session; Friday, June 15, 2018; 5:30-7:00 p.m. CEST
Venetoclax Monotherapy and Combined with Dexamethasone as Targeted Therapy for Relapsed/Refractory t(11;14) Multiple Myeloma. Kaufman et al.; Abstract PS1317; Poster Session; Saturday, June 16, 2018; 5:30-7:00 p.m. CEST
Venetoclax in ALL
Venetoclax and Navitoclax with Chemotherapy is Efficacious in Patients with Relapsed Acute Lymphoblastic Leukemia. Alexander et al.; Abstract PS928; Poster Session, Saturday, June 16, 2018; 5:30-7:00 p.m. CEST
The EHA (Free EHA Whitepaper) 2018 Annual Congress abstracts are available at www.ehaweb.org.
About VENCLYXTO (venetoclax)
VENCLYXTO (venetoclax), an oral B-cell lymphoma-2 (BCL-2) inhibitor, is indicated for the treatment of chronic lymphocytic leukemia (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; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.4 It is also being evaluated for the treatment of patients with various blood cancer types.4,5,6,7,8 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.4 VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.4
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 with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other cancers.
Venetoclax is currently approved in the European Union, Switzerland, Argentina, Australia, Mexico, Puerto Rico, Israel, USA, and Canada. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.
For more information on AbbVie’s research in oncology, please read, "Breaking the Rules of Science to Treat Cancer," on www.abbvie.com.
Important Venclyxto (venetoclax) EU Safety Information
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 tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as VENCLYXTO efficacy may be reduced.
Special Warnings & Precautions for Use
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week 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. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS. Blood chemistries should be monitored and abnormalities managed promptly. More intensive measures (including IV hydration, frequent monitoring and hospitalization) should be employed as overall risk increases.
Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period.
Live vaccines should not be administered during treatment or thereafter until B-cell recovery.
Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. 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, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.
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
The most commonly occurring adverse reactions (>=20%) of any grade were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, upper respiratory tract infection, fatigue, hyperphosphatemia, vomiting and constipation.
The most frequently occurring adverse reactions (>=2%) were pneumonia, febrile neutropenia and TLS.
Discontinuations due to adverse reactions occurred in 9.1% of patients and dosage adjustments due to adverse reactions occurred in 11.8% of patients.
Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS. 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. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.
VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Advise nursing women to discontinue breastfeeding during treatment.
This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.