Monitor and evaluate patients for fever and infections and treat appropriately. Imbruvica comes as capsules, tablets, and oral suspension. Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. IMBRUVICA (ibrutinib) inhibits BTK to disrupt 3 key B-cell processes* 1. Adult patients with Waldenstrm's macroglobulinemia (WM). Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. You are leaving the patient and caregiver site and entering the US Healthcare professional site. IMBRUVICA (ibrutinib) inhibits BTK to disrupt 3 key B-cell processes* 1. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Binsky I, Lantner F, Grabovsky V, et al. imbruvica Dosage is a powerful low-molecular weight inhibitor of Bruton's tyrosine kinase (TCB). Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). cGVHD: The most common adverse reactions (20%) in adult or pediatric patients with cGVHD were fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal pain (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), abdominal pain (23%), pneumonia (23%), and headache (21%). IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Abstract 923. The MCL and MZL indications are approved under accelerated approval based on overall response rate. The MCL and MZL indications are approved under accelerated approval based on overall response rate. The mechanism for the bleeding events is not well understood. Monitor patients closely and treat as appropriate. TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. Images courtesy of Janssen Biotech. Site is running on IP address 159.180.132.176, host name 159.180.132.176 (North Chicago United States) ping response time 13ms Good ping.Current Global rank is 5,239,465, site estimated value 408$ Imbruvica (ibrutinib) is an oral Brutons tyrosine kinase (BTK) inhibitor indicated for the treatment of mantle cell lymphoma (MCL) patients that previously received at least one therapy. TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. This indication is approved under accelerated approval based on overall response rate. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. The mechanism for the bleeding events is not well understood. Inhibits adhesion 1,6-11 3. B-cell malignancies: The most common adverse reactions (30%) in adult patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (54.5%)*, diarrhea (43.8%), fatigue (39.1%), musculoskeletal pain (38.8%), neutropenia (38.6%)*, rash (35.8%), anemia (35.0%)*, and bruising (32.0%). 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics PRC-09921. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Monitor and evaluate patients for fever and infections and treat appropriately. Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or greater cardiac failure was reported in 1.3% of 4,896 patients who received IMBRUVICA in clinical trials, including in patients who received IMBRUVICA in unapproved monotherapy or combination regimens. Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of adult patients had a dose reduction due to adverse reactions. It forms a covalent bond with a cysteine residue in the active site of BTK (Cys481), leading to its inhibition. The enzyme in your body that Imbruvica targets is called Bruton's tyrosine kinase (BTK). Patients with cardiac comorbidities may be at greater risk of these events. Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA in clinical trials. Mantle cell lymphoma (MCL) is a slow growing blood cancer. Kurtova AV, Tamayo AT, Ford RJ, Burger JA. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenstrm's macroglobulinemia. The primary outcome measure of the study was to measure the number of participants with a response to the drug. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. As demonstrated by in vitro and in vivo studies. The pharmaceutical industry's most comprehensive news and information delivered every month. See dose modification guidelines in USPI sections 2.3 and 7.1. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Previously Treated Marginal Zone Lymphoma*, Previously Treated Chronic Graft Versus Host Disease. Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Regulatory Classification B Presentation/Packing Form Imbruvica hard cap 140 mg Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm. Chang BY, Francesco M, de Rooij MFM, et al. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Summary. Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. The drug is co-marketed in the US by Pharmacyclics and Janssen Biotech. 1 Hemorrhage Honigberg LA, Smith AM, Sirisawad M, et al. Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Reduce recommended dose when administering IMBRUVICA to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilberts syndrome). Most commonly, these include: 1 Diarrhea Tiredness Muscle and bone pain Rash Bruising Mouth sores ( stomatitis) Muscle spasms Nausea Pneumonia Severe In rarer cases, more severe side effects crop up. de Rooij MFM, Kuil A, Geest CR, et al. Correlation with clinical effect has not been established. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. It is a rare form of non-Hodgkin Lymphoma (NHL). Ibrutinib inhibits malignant cell adhesion and migration and reduces tumor burden in lymph node and bone marrow in a murine model of mantle cell dissemination and progression. Grade 3 or greater hypertension occurred in 8% of patients. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. 12.1 Mechanism of Action Ibrutinib is a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA treatment. BTK=Bruton's tyrosine kinase. . Ponader S, Chen S-S, Buggy JJ, et al. 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. Janssen conducted the Phase II clinical trials between February 2011 and June 2013. Honigberg LA, Smith AM, Sirisawad M, et al. Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. IMBRUVICA (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA treatment. Cytopenias: In 645 patients with B-cell malignancies who received IMBRUVICA as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 2.8%, based on laboratory measurements. If your healthcare provider prescribes IMBRUVICA capsules or tablets: Swallow IMBRUVICA capsules or tablets whole with a glass of water. Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe hepatic impairment. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death:Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Drink plenty of liquids while you are taking Imbruvica. Pediatric Use: The safety and effectiveness of IMBRUVICA have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. Mechanism of action Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. In comparison to ibrutinib, acalabrutinib was associated with an overall higher occurrence rate of headache, cough and fatigue. The median duration of response was 17.5 months. "Mantle cell lymphoma is a rare type of blood cancer of the B cells. For any questions about the Pharmacyclics Privacy Policy, please visit www.pharmacyclics.com. Correlation with clinical effect has not been established. Adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. We encourage you to read the Privacy Policy of every website you visit. Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA. Thank you for subscribing to Clinical Trials Arena. Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA increases the risk of major hemorrhage. . The safety and effectiveness of IMBRUVICA in pediatric patients have not been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL or in patients with mature B-cell non-Hodgkin lymphoma. This indication is approved under accelerated approval based on overall response rate. Swallow the tablet or capsule whole and do not crush, chew, break, or open it. Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe hepatic impairment. With supply chain disruptions and inflation creating new challenges for delivery teams, design-build projects are booming. Avoid concomitant use of other strong CYP3A inhibitors. Pharmacyclics LLC recognizes that the Internet is a global communication medium; however laws, regulatory requirements, and medical practices vary from country to country. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Key drug pipeline and competitive landscape changes based on the latest clinical activity, sent every Tuesday. Inhibits adhesion 1,6-11 3. Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). Modulates chemotaxis and trafficking 1,5,7,9,11-14 * As demonstrated by in vitro and in vivo studies. Abstract 923. We encourage you to read the Privacy Policy of every website you visit. View Imbruvica mechanism of action for pharmacodynamics and pharmacokinetics details. Egress of CD19+CD5+ cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. IMBRUVICA (ibrutinib) inhibits BTK to disrupt 3 key B-cell processes* 1. The safety and effectiveness of IMBRUVICA in pediatric patients have not been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL or in patients with mature B-cell non-Hodgkin lymphoma. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). The most common Grade 3 or 4 non-haematological adverse reactions found during the clinical study included pneumonia, abdominal pain, atrial fibrillation, diarrhoea, skin infections, and fatigue. *Treatment-emergent decreases (all grades) were based on laboratory measurements. Adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month after the last dose. The exact mechanism of action is unclear but it appears that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor under arterial flow 40, 41. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA without antiplatelet or anticoagulant therapy experienced major hemorrhage. TKB, a member of the Tes family of kinases, acts as an important signal molecule in metabolic pathways associated with the signal activity of antigenic B-cell receptors (BCR) and cytokine receptors. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Previously Treated Marginal Zone Lymphoma*, Previously Treated Chronic Graft Versus Host Disease. Though the precise mechanism of action of the drug is not known completely, it is presumed the drug works by stopping the malignant B-cell proliferation and survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Cardiac Arrhythmias, Cardiac Failure, and Sudden Death:Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA. Imbruvica was developed under the FDAs accelerated approval programme. Herman SEM, Gordon AL, Hertlein E, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. The MCL and MZL indications are approved under accelerated approval based on overall response rate. The drug is available in the form of 140mg capsules for oral administration, and sold in 90 and 120 capsule boxes. The FDA granted approval for Imbruvica for the treatment of MCL patients in November 2013. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. Monitor blood pressure in patients treated with IMBRUVICA, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension. Ibrutinib forms a covalent bond with the cysteine residue (Cys 481) in the active centre of the TKB, resulting in persistent inhibition of enzymatic activity. Chang BY, Francesco M, Steggerda S, et al. Adult patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy. Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion. Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA in clinical trials. Adult patients with Waldenstrm's macroglobulinemia (WM). Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA. Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Imbruvica (ibrutinib) is a once-daily oral medicine that works differently than chemotherapy as it blocks the Bruton's tyrosine kinase (BTK) protein. Mechanism: Related to mechanism of action; inhibits B-cell function, increasing the risk for opportunistic infections, . It is a rare form of non-Hodgkin Lymphoma (NHL). Patients who received ibrutinib also lived . Monitor and evaluate patients for fever and infections and treat appropriately. Adverse reactions also lead to reduction in Imbruvica dose levels in 14% of patients during the clinical trials. *Treatment-emergent decreases (all grades) were based on laboratory measurements. IMBRUVICA blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. Take Imbruvica 1 time a day at about the same time each day. Increased ibrutinib concentrations may increase the risk of drug-related toxicity. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Cell trafficking in chronic lymphocytic leukemia. Image courtesy of Nephron. Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of adult patients had a dose reduction due to adverse reactions. The drug was jointly developed by Janssen Biotech and Pharmacyclics. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Egress of CD19+CD5+ cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Adult patients with Waldenstrm's macroglobulinemia (WM). Bleeding events of any gradeincluding bruising and petechiaeoccurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA, respectively. Inhibits proliferation and survival 1-6 2. The NDA for Imbruvica was accepted by the FDA in August 2013. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Bruton's tyrosine kinase (BTK) inhibitors, Please enter a work/business email address. IMBRUVICA(ibrutinib) is covered by U.S. Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA without antiplatelet or anticoagulant therapy experienced major hemorrhage. Davids MS, Burger JA. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating . For any questions about the Pharmacyclics Privacy Policy, please visit www.pharmacyclics.com. Inhibits proliferation and survival 1-6 2. Mechanism of Action Imbruvica (ibrutinib) is an orally available, selective inhibitor of Bruton's tyrosine kinase (Btk). Patents, which are listed in FDA's Orange Book (available athttps://www.accessdata.fda.gov/scripts/cder/ob/default.cfm). The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Pharmacyclics LLC recognizes that the Internet is a global communication medium; however laws, regulatory requirements, and medical practices vary from country to country. Pediatric Use: The safety and effectiveness of IMBRUVICA have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. As demonstrated byin vitroandin vivostudies. IMBRUVICA is a kinase inhibitor indicated for the treatment of: Your use of the information on this site is subject to the terms of theLegal Noticeand newPrivacy Policyof Pharmacyclics LLC. Used in the treatment of cancer. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. I consent to GlobalData UK Limited collecting my details provided via this form in accordance with the, Specialty drug launch strategy and operations, The next chapter of clinical trial services, KYNMOBI for the Treatment of OFF episodes in Parkinsons Disease, USA, Sotyktu (deucravacitinib) to Treat Moderate to Severe Plaque Psoriasis, USA, QUVIVIQ (daridorexant) for the Treatment of Insomnia, USA, Pfizer and BioNTech report data from Omicron-based Covid-19 booster trial, Shuttle engages CRO Theradex for brain tumour treatment trial, Inato improves platform to boost trial access and inclusion. ", Hard data and deep insights on clinical trials strategy & operations, Receive our newsletter - data, insights and analysis delivered to you. Patients with cGVHD: Avoid use of IMBRUVICA in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilberts syndrome). Ponader S, Chen S-S, Buggy JJ, et al. The information contained in this site is intended for US Healthcare professionals only. You are leaving the patient and caregiver site and entering the US Healthcare professional site. Patients with cGVHD: Avoid use of IMBRUVICA in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilberts syndrome). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. In patients with mild or moderate impairment, reduce recommended IMBRUVICA dose and monitor more frequently for adverse reactions of IMBRUVICA. A first-in-class, oral covalent BTK inhibitor, Dosing Modifications for Adverse Reactions, Support & Resources: Educational Materials, https://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA without antiplatelet or anticoagulant therapy experienced major hemorrhage. We encourage you to read the Privacy Policy of every website you visit. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. Monitor blood pressure in patients treated with IMBRUVICA, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension. Patients were administered with a recommended dose of Imbruvica 560mg (four 140mg capsules) orally once daily. Major hemorrhage ( Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post- Avoid concomitant use of other strong CYP3A inhibitors. IMBRUVICA(ibrutinib) is covered by U.S. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. This site is published by Pharmacyclics LLC which has developed the content in conjunction with Janssen Biotech, Inc. Any information that is collected on this site may be shared between Pharmacyclics LLC and Janssen Biotech, Inc.