On November 20, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that data from nearly 40 abstracts, including 13 oral presentations and more than 20 poster presentations, will be presented during the upcoming 60th ASH (Free ASH Whitepaper) Annual Meeting & Exposition, December 1-4, in San Diego (Press release, AbbVie, NOV 20, 2018, View Source [SID1234531490]).
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Investigators will present data from the Phase 3 iLLUMINATE trial, which evaluates the safety and efficacy of ibrutinib (Imbruvica) in combination with obinutuzumab vs. chlorambucil in combination with obinutuzumab in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not received a prior treatment. In addition, seven-year data on patients treated with ibrutinib will be presented, marking the longest follow-up study for a Bruton’s tyrosine kinase (BTK) inhibitor. IMBRUVICA is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
"AbbVie’s data at the annual ASH (Free ASH Whitepaper) meeting shows the progress we’re making in collaboration with scientists, doctors and patients, toward transforming the standard of care in numerous blood cancers," said Neil Gallagher, M.D., Ph.D., vice president, head of global oncology development, AbbVie. "We are pleased to share important updates from our ibrutinib and venetoclax programs, where we continue to see the positive impact these two first-in-class medicines are having in treating blood cancers."
Among the oral presentations is one featuring updated data from the pivotal Phase 3 MURANO study of venetoclax in combination with rituximab in patients with relapsed/refractory (R/R) CLL, providing an additional year of follow-up data of sustained benefits (progression-free survival and minimal residual disease) for patients taking the fixed-duration treatment regimen of approximately two years.1
AbbVie also will present data from multiple studies evaluating its compounds alone or in novel combinations across other blood cancers and hematologic diseases. These include CLL, acute myeloid leukemia (AML), multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM), among others.
Details about AbbVie’s oral presentations are as follows:
Abstract
Oral Presentation Timing
Ibrutinib
Ibrutinib Treatment in Waldenström’s Macroglobulinemia: Follow-up Efficacy and Safety from the iNNOVATE Study; Buske et al.; Abstract #149
Saturday, December 1; 1:00 p.m. PT
The iR2 Regimen (Ibrutinib, Lenalidomide, and Rituximab) Is Active with a Manageable Safety Profile in Patients with Relapsed/Refractory Non-Germinal Center-like Diffuse Large B-Cell Lymphoma; Ramchandren et al.; Abstract #402
Sunday, December 2; 1:15 p.m. PT
Up to 7 Years of Follow-up of Single-Agent Ibrutinib in the Phase 1b/2 PCYC-1102 Trial of First Line and Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Byrd et al.; Abstract #3133
Sunday, December 2; 6:00-8:00 p.m. PT*
Ibrutinib + Obinutuzumab Versus Chlorambucil + Obinutuzumab as First-Line Treatment in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL): Results from Phase 3 iLLUMINATE; Moreno et al.; Abstract #691
Monday, December 3; 10:30 a.m. PT
Venetoclax
Durability of Responses on Continuous Therapy and Following Drug Cessation in Deep Responders with Venetoclax and Rituximab; Brander et al.; Abstract #183
Saturday, December 1; 2:30 p.m. PT
MURANO Trial Establishes Feasibility of Time-Limited Venetoclax-Rituximab (VenR) Combination Therapy in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL); Seymour et al.; Abstract #184
Saturday, December 1; 2:45 p.m. PT
Venetoclax with Low-Dose Cytarabine Induces Rapid, Deep, and Durable Responses in Previously Untreated Older Adults with AML Ineligible for Intensive Chemotherapy; Wei et al.; Abstract #284
Sunday, December 2; 7:45 a.m. PT
Venetoclax in Combination with Hypomethylating Agents Induces Rapid, Deep, and Durable Responses in Patients with AML Ineligible for Intensive Therapy; Pollyea et al.; Abstract #285
Sunday, December 2; 8:00 a.m. PT
Phase 2 Study of Venetoclax Plus Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma; Costa et al.; Abstract #303
Sunday, December 2; 8:00 a.m. PT
Safety and Efficacy of Venetoclax Combined with Rituximab, Ifosfamide, Carboplatin and Etoposide Chemoimmunotherapy (VICER) for Treatment of Relapsed Diffuse Large B Cell Lymphoma: Results from the Phase 1 Study; Caimi et al.; Abstract #397
Sunday, December 2; 12:00 p.m. PT
Combination of Enasidenib and Venetoclax Shows Superior Anti-Leukemic Activity Against IDH2 Mutated AML in Patient-Derived Xenograft Models; Cathelin et al.; Abstract #562
Monday, December 3; 7:45 a.m. PT
First Prospective Data on Impact of Minimal Residual Disease on Long-Term Clinical Outcomes after Venetoclax Plus Rituximab Versus Bendamustine Plus Rituximab: Phase 3 MURANO Study; Kater et al.; Abstract #695
Monday, December 3; 11:30 a.m. PT
Venetoclax Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) Improves Outcomes in BCL-2 Positive First-Line Diffuse Large B-Cell Lymphoma (DLBCL): First Safety, Efficacy and Biomarker Analyses from the Phase 2 CAVALLI Study; Morschhauser et al.; Abstract #782
Monday, December 3; 3:00 p.m. PT
Safety, Efficacy, Pharmacokinetic (PK) and Biomarker Analysis of BCL-2 Inhibitor Venetoclax (Ven) Plus MDM2 Inhibitor Idasanutlin (idasa) in Patients (pts) with Relapsed or Refractory (R/R) AML: A Phase Ib, Non-Randomized, Open-Label Study; Daver et al.; Abstract #767
Monday, December 3; 3:45 p.m. PT
*Poster Presentation
About VENCLEXTA/VENCLYXTO (venetoclax)
VENCLEXTA/VENCLYXTO (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein.2 In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis.2 VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.
VENCLEXTA/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.
VENCLEXTA/VENCLYXTO is approved in more than 50 countries, including the U.S. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.
Important VENCLEXTA (venetoclax tablets) US Safety Information2
What is the most important information I should know about VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your health care provider will do tests to check your risk of getting TLS before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Your health care provider will do blood tests in your first 5 weeks of treatment to check you for TLS during treatment with VENCLEXTA. It is important to keep your appointments for blood tests. Tell your health care provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.
Drink plenty of water when taking VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.
Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased tumor lysis syndrome.
Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other, causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your health care provider.
Before taking VENCLEXTA, tell your health care provider about all of your medical conditions, including if you:
Have kidney or liver problems.
Have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
Have a history of high uric acid levels in your blood or gout.
Are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during or after treatment with VENCLEXTA until your health care provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your health care provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
Are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your health care provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your health care provider right away.
Are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.
What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Low white blood cell count (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your health care provider will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your health care provider right away if you have a fever or any signs of an infection while taking VENCLEXTA.
The most common side effects of VENCLEXTA when used in combination with rituximab include low white blood cell count, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.
The most common side effects of VENCLEXTA when used alone include low white blood cell count, diarrhea, nausea, upper respiratory tract infection, low red blood cell count, tiredness, low platelet count, muscle and joint pain, swelling of your arms, legs, hands, and feet, and cough.
VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your health care provider if you have concerns about fertility.
These are not all the possible side effects of VENCLEXTA. Tell your health care provider if you have any side effect that bothers you or that does not go away.
People are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information.
About IMBRUVICA (ibrutinib) in the U.S.3
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that mainly works by inhibiting a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.
IMBRUVICA is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
IMBRUVICA is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host disease (cGVHD).3
IMBRUVICA was first approved for adult patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in adult CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for adult CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for adult patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for adult patients with CLL/SLL.
In January 2017, IMBRUVICA was approved for adult patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
In August 2017, IMBRUVICA was approved for adult patients with cGVHD that failed to respond to one or more lines of systemic therapy.
In August 2018, IMBRUVICA plus rituximab was approved for adult patients with WM.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.5 IMBRUVICA was one of the first medicines to receive FDA approval via the new Breakthrough Therapy Designation pathway.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with more than 130 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. To date, more than 120,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in 3% of patients, with fatalities occurring in 0.3% of 1,011 patients exposed to IMBRUVICA in clinical trials. Bleeding events of any grade, including bruising and petechiae, occurred in 44% of patients treated with IMBRUVICA.
The mechanism for the bleeding events is not well understood.
IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding.
Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 24% of 1,011 patients exposed to IMBRUVICA in clinical trials. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.
Monitor and evaluate patients for fever and infections and treat appropriately.
Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (23%), thrombocytopenia (8%), and anemia (3%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA.
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4% of 1,011 patients exposed to IMBRUVICA in clinical trials. These events have occurred particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac arrhythmias.
Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.
Hypertension: Hypertension has occurred in 12% of 1,011 patients treated with IMBRUVICA in clinical trials with a median time to onset of 5 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.
Second Primary Malignancies: Other malignancies (9%) including non-skin carcinomas (2%) have occurred in 1,011 patients treated with IMBRUVICA in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.
Monitor patients closely and treat as appropriate.
Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.
ADVERSE REACTIONS
B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, neutropenia (58%)*, diarrhea (42%), anemia (39%)*, rash (31%), musculoskeletal pain (31%), bruising (31%), nausea (28%), fatigue (27%), hemorrhage (23%), and pyrexia (20%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (36%)*, thrombocytopenia (15%)*, and pneumonia (10%).
Approximately 6% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions.
cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).
The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%)*, pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).
Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.
*Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse reactions.
DRUG INTERACTIONS
CYP3A Inhibitors: Dose adjustments may be recommended.
CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.
SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe baseline hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose.