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Official Janssen Oncology Online Press Kit for the 58th ASH Annual Meeting
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Late-breaking Phase 2 Ibrutinib Study in Chronic Graft-Versus-Host-Disease (cGVHD) Showed Complete or Partial Response in Up to Two-Thirds of Steroid Dependent or Refractory Patients
Data at the American Society of Hematology Annual Meeting highlight potential role of ibrutinib therapy beyond hematologic cancers
cGVHD is a major cause of stem cell or bone marrow transplant-related illness, death and functional impairment with no FDA-approved treatments specifically for this condition1
This release corresponds to abstract #LBA-3
PR Newswire, SAN DIEGO, CA and RARITAN, NJ, December 6, 2016 — Janssen Research & Development, LLC (Janssen) today announced Phase 2 ibrutinib (IMBRUVICA®) data showing encouraging results in patients with chronic graft-versus-host-disease (cGVHD), a life-threatening consequence of stem cell or bone marrow transplant, who failed prior systemic therapy.2 Study findings indicate ibrutinib demonstrated clinically meaningful and durable responses and reduced symptom severity, with an overall response rate (ORR) of 67% in patients with cGVHD.3 The late-breaking data will be presented today in an oral session at the 58th American Society of Hematology (ASH) Annual Meeting in San Diego, Calif. (abstract #LBA-3). IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.
At a median follow-up of 14 months (0.5-25) in 42 patients, one third of all responders achieved a complete response (CR); 71% of patients with a complete or partial response showed a sustained response of at least 5 months. Over the course of the study, 61% of responders experienced a clinically meaningful improvement in symptoms, as measured by at least a 7-point decrease in Lee Symptom Scale score. Additionally, a reduction in steroid dose <0.15 mg/kg/day was reached in 62% of patients with a complete or partial response. Twelve patients (29%) remained on treatment at the time of this analysis.3
“There is an urgent need for effective new therapies for patients with steroid-resistant chronic graft-versus-host-disease, a condition that can be incapacitating and even fatal when it is not controlled,” said lead investigator David Miklos, M.D., Ph.D., Associate Professor of Medicine, Blood and Marrow Transplantation, Stanford University.* “These data are promising as they suggest that ibrutinib may offer a new approach for managing this common post-transplant complication.”Read More
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 up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half 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 postsurgery depending upon the type of surgery and the risk of bleeding.
Infections - Fatal and nonfatal infections have occurred with IMBRUVICA® therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA®. Evaluate patients for fever and infections and treat appropriately.
Cytopenias - Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA®. Monitor complete blood counts monthly.
Atrial Fibrillation - Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA®, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA® treatment and follow dose modification guidelines.
Hypertension - Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA® with a median time to onset of 4.6 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 antihypertensive medications and/or initiate antihypertensive treatment as appropriate.
Second Primary Malignancies - Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA®. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).
Tumor Lysis Syndrome - Tumor lysis syndrome has been infrequently reported with IMBRUVICA® therapy. Assess the baseline risk (eg, 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.
ADVERSE REACTIONS The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were neutropenia* (64%), thrombocytopenia* (63%), diarrhea (43%), anemia*(41%), musculoskeletal pain (30%), rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia (21%).
*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).
The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%). Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.
Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.
CYP3A Inhibitors - Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA® dose.
CYP3A Inducers - Avoid coadministration with strong CYP3A inducers.
Hepatic Impairment - Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA® dose.
Please see Full Prescribing Information: https://www.imbruvica.com/prescribing-information.