What is ibrutinib used to treat?
Ibrutinib is approved to treat: Chronic lymphocytic leukemia and small lymphocytic lymphoma in adults. Mantle cell lymphoma in adults who have received at least one other treatment.¹ Marginal zone lymphoma. It is used in adults who have received at least one other CD20 - targeted therapy .¹
Can I continue to take ibrutinib If I have surgery?
The exception is, if surgery is required or other blood thinners are used, then continuing to take ibrutinib can increase the risk of serious bleeds. For blood thinners, the most dangerous one is Coumadin and most clinical trials performed with ibrutinib excluded patients taking this. I am having a surgical procedure.
Can I lower the dose of ibrutinib for diarrhea?
Lowering the dose or holding ibrutinib is not something that should be done unless the symptoms of diarrhea cannot be controlled. In general, diarrhea, rash, and also heart burn side effects diminish over the first 1-2 months of therapy. I have had a good response to ibrutinib over the past 6 months and now it has been suggested to stop treatment.
How effective is ibrutinib in the treatment of B-cell carcinoma?
Preclinical studies have shown that ibrutinib effectively inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro.
What type of therapy is ibrutinib?
Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells.
Is ibrutinib considered chemotherapy?
Ibrutinib is not a chemotherapy drug but one of what are termed "targeted therapies." Targeted therapy is the result of years of research dedicated to understanding the differences between cancer cells and normal cells.
Is ibrutinib an immunotherapy?
This is a type of immunotherapy that works by activating your immune system to fight the cancer. Imbruvica can also be used in the treatment of CLL or SLL in people with a 17p deletion.
Is ibrutinib a targeted therapy?
Ibrutinib, a new oral targeted therapy drug, is the first agent that binds to the Bruton's tyrosine kinases and inhibits overgrowth of B cells. In blocking this overgrowth, ibrutinib has been shown to achieve lengthy remissions for patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).
Is ibrutinib a biologic?
Biologic agents are increasingly used in the treatment of CLL, typically in combination with chemotherapeutic agents. These biologic agents include several monoclonal antibodies (eg, rituximab), the P13K inhibitor duvelisib, and the Bruton tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib.
Is ibrutinib an immunosuppressant?
Ibrutinib, an approved drug for B-cell lineages and chronic graft versus host disease (cGVHD), exhibits immunosuppressive efficacy in autoimmune diseases. Ibrutinib's potential as an immunosuppressant in organ transplantation has not been investigated to date.
Is ibrutinib a cytotoxic?
BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib and lenalidomide activities through NF-κB. Cell Signal.
How long can a person take ibrutinib?
Imbruvica (ibrutinib) is usually continued indefinitely if it is being well tolerated, there is limited disease progression, and toxicity has not occurred. In some people, very good partial clinical responses may occur within three to six months.
Does ibrutinib cure CLL?
So far, ibrutinib has led to few complete remissions. The drug tamps down CLL, but so far doesn't cure it, Burger reports. However, complete response rates are increasing in the group of patients taking the ibrutinib/rituximab combination.
Is Imbruvica a monoclonal antibody?
Ibrutinib-Monoclonal Antibody Combinations. Ibrutinib has been studied in combination with rituximab, a genetically engineered chimeric human monoclonal antibody directed against CD20 antigen. Rituximab has been widely used as monotherapy and in combination with chemotherapy in CLL.
Is rituximab a monoclonal antibody?
Rituximab is a chimeric mouse/human monoclonal antibody (mAb) therapy with binding specificity to CD20. It was the first therapeutic antibody approved for oncology patients and was the top-selling oncology drug for nearly a decade with sales reaching $8.58 billion in 2016.
What is the newest treatment for CLL?
In May 2019, the FDA approved venetoclax (Venclexta) in combination with obinutuzumab (Gazyva) to treat people with previously untreated CLL as a chemotherapy-free option. In April 2020, the FDA approved a combination therapy of rituximab (Rituxan) and ibrutinib (Imbruvica) for adult patients with chronic CLL.
Can ibrutinib be stopped safely?
Stopping ibrutinib can result in a disease flare-up in patients with chronic lymphocytic leukemia (CLL). A 2020 study in The Oncologist found that...
Does ibrutinib cause hair loss?
Hair loss (alopecia) has not been noted as a side effect of ibrutinib (Imbuvica) in the product label. Textural hair changes (softening, straighten...
Acalabrutinib vs. ibrutinib: How do they compare?
A 2021 phase III study in the Journal of Clinical Oncology found that while both medications have similar efficacy, acalabrutinib was better tolera...
Why are drugs studied?
Drugs are often studied to find out if they can help treat or prevent conditions other than the ones they are approved for. This patient information sheet applies only to approved uses of the drug. However, much of the information may also apply to unapproved uses that are being studied.
Is the drug information on this page educational?
Important: The drug information on this page is meant to be educational. It is not a substitute for medical advice. The information may not cover all possible uses, actions, interactions, or side effects of this drug, or precautions to be taken while using it. Please see your health care professional for more information about your specific medical condition and the use of this drug.
Is ibrutinib used for cancer?
Use in Cancer. Ibrutinib is approved to treat: Chronic lymphocytic leukemia and small lymphocytic lymphoma in adults. It is used alone or with other drugs. Mantle cell lymphoma in adults who have received at least one other treatment.¹. Marginal zone lymphoma.
What is ibrutinib used for?
Uses of Ibrutinib Tablets: It is used to treat types of leukemia and lymphoma. It is used to treat Waldenstroms' macroglobulinemia (WM). It is used to treat graft versus host effects after a bone marrow transplant. It may be given to you for other reasons.
How to take ibrutinib?
Take this medicine (ibrutinib tablets) at the same time of day. Take with a full glass of water. Keep taking this medicine (ibrutinib tablets) as you have been told by your doctor or other health care provider, even if you feel well. Avoid grapefruit and grapefruit juice .
When to take missed meds?
Take a missed dose as soon as you think about it on the same day you missed the dose.
Does ibrutinib cause high blood pressure?
High blood pressure has happened with this medicine (ibrutinib tablets). Have your blood pressure checked as you have been told by your doctor.
Can Ibrutinib cause yellow skin?
If you are 65 or older, use this medicine (ibrutinib tablets) with care. You could have more side effects.
Can ibrutinib cause brain damage?
It may cause disability or can be deadly. Tell your doctor right away if you have signs like confusion, memory problems, low mood ( depression ), change in the way you act, change in strength on 1 side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight.
Can Ibrutinib cause diarrhea?
Constipation, diarrhea, throwing up, and upset stomach are common with this medicine (ibrutinib tablets). If these happen, talk with your doctor about ways to lower these side effects. Call your doctor right away if any of these effects bother you, do not go away, or get very bad.
What is ibrutinib used for?
Ibrutinib is used to treat chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia, and as a second-line treatment for mantle cell lymphoma, marginal zone lymphoma, and chronic graft vs host disease. BTK inhibition by ibrutinib impairs the BCR signalling pathway, which is a key dependency of malignant B cells, ...
When was ibrutinib approved?
It was approved by the US Food and Drug Administration (FDA) on November 13, 2013, for the treatment of mantle cell lymphoma. On February 12, 2014, the FDA expanded the approved use of ibrutinib to chronic lymphocytic leukemia (CLL). It was approved for Waldenström's macroglobulinemia in 2015. In March 2015, Pharmacyclics and AbbVie agreed ...
What is the role of ibrutinib in BTK?
BTK is an important signalling molecule of the B-cell antigen receptor (BCR) pathway, which is plays a role in the pathogenesis of several B-cell malignancies including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and chronic lymphocytic leukemia (CLL). Preclinical studies have shown that ibrutinib effectively inhibits malignant B-cell proliferation and survival in vivo as well as cell migration and substrate adhesion in vitro.
How much does ibrutinib cost?
The typical cost of ibrutinib in the United States is about $148,000 a year . Preliminary PK/PD focused research found that people could potentially be put on lower and less expensive regimen of ibrutinib without losing efficiency; however, no data showing efficiency of lower doses has been published.
When did Abbvie buy Pharmacyclics?
In March 2015, Pharmacyclics and AbbVie agreed that Abbvie would acquire Pharmacyclics for $21 billion; the deal was completed that May.
When was Ibrutinib added to the Australian Pharmaceutical Benefits Scheme?
Ibrutinib was added to the Australian Pharmaceutical Benefits Scheme in 2018.
Is ibrutinib a tablet?
In February 2018, a tablet formulation of ibrutinib was approved for use in the United States. In August 2018, ibrutinib in combination with rituximab was approved in the United States for the treatment of adults with Waldenström's macroglobulinemia (WM), a rare and incurable type of non-Hodgkin's lymphoma (NHL).
How often is ibrutinib given?
Participants were randomly assigned to receive ibrutinib, which was taken orally once daily, or ofatumumab, which was given by intravenous infusion once weekly for up to 24 weeks. Patients assigned to the ofatumumab group whose disease progressed during the trial could cross over and receive ibrutinib.
What is the function of ibrutinib?
Ibrutinib inhibits the action of a protein called Bruton tyrosine kinase. This protein is involved in a key signaling pathway controlled by the B-cell receptor that is important for the growth and survival of B cells.
How does Ofatumumab work?
The two drugs work in different ways. Ofatumumab is a monoclonal antibody that binds to the CD20 antigen on the CLL/SLL cells. This binding directly induces cancer cell death; it also triggers the immune system to destroy the cells. Ibrutinib inhibits the action of a protein called Bruton tyrosine kinase.
How long does it take to follow up on ibrutinib?
The median follow-up in the trial was 9.4 months. Fewer than half the patients who received ibrutinib experienced a worsening of the disease or died, whereas half of patients who received ofatumumab had disease progression or died after 8.1 months. Thus, patients who received ibrutinib had a 78 percent reduction in the risk of disease progression or death compared with those in the ofatumumab group.
What are the side effects of ibrutinib?
The most common side effects in patients taking ibrutinib were diarrhea, fatigue, fever, and nausea. More patients in the ibrutinib group than in the ofatumumab group had at least one adverse event of grade 3 or higher (57 percent versus 47 percent). Adverse events (grade 3 or higher) that occurred more frequently in patients taking ibrutinib than in those taking ofatumumab included diarrhea (4 percent versus 2 percent) and irregular or rapid heart rate (3 percent versus 0 percent). Bleeding-related adverse events of any grade were also more common in the ibrutinib group than in the ofatumumab group (44 percent versus 12 percent). Ocular symptoms, including blurred vision and cataracts, were also more common in patients who received ibrutinib, the authors reported.
Does ofatumumab have a lower response rate?
Also complicating the analysis of response rate was the finding that the patients treated with ofatumumab had a substantially lower response rate than was seen in the clinical trial that led to FDA's approval of this therapy. The RESONATE investigators noted that this difference likely reflects their use of serial computed tomography (CT) scans to assess patient response, which the previous trial did not. In patients with CLL, CT scans are now commonly used to confirm suspected treatment responses by assessing whether there is a reduction in the size of patients' lymph nodes and spleen.
Is ibrutinib more common than ofatumumab?
Bleeding-related adverse events of any grade were also more common in the ibrutinib group than in the ofatumumab group (44 percent versus 12 percent). Ocular symptoms, including blurred vision and cataracts, were also more common in patients who received ibrutinib, the authors reported.
How does ibrutinib work?
Ibrutinib works as an antiplatelet medication similar to aspirin. The time it takes to heal from a cut may take longer than before taking ibrutinib. Additionally, you may notice more bruising as a result of taking ibrutinib. Let your care team know if you have any excess bruising or bleeding of any kind, including nose bleeds, bleeding gums or blood in your urine or stool. In some cases this medication can cause serious bleeding. Call your provider right away if you have bleeding that is not stopping. Inform your doctor of any medical procedures or dental procedures/cleanings because ibrutinib will need to be held for a period of time before and after the procedure. Taking anti-coagulant medications or anti-platelet agents can increase the risk of major bleeding so you should make sure your provider is aware of all medications that you are taking.
What is ibrutinib kinase inhibitor?
About: Ibrutinib (Imbruvica®) Ibrutinib is a type of targeted therapy called a kinase inhibitor. A kinase is an enzyme that promotes cell growth. There are many types of kinases, which control different phases of cell growth. This medication interferes with the function of Bruton's tyrosine kinase ...
Does ibrutinib interfere with BTK?
By interfering with BTK, ibrutinib interferes with the growth of the cancerous B cells.
How long after starting ibrutinib can you have surgery?
For this reason, I generally recommend putting off elective surgery until 9-12 months after starting ibrutinib when possible.
How long should I hold ibrutinib?
How long should I hold my ibrutinib and what should be expected when this is stopped? In general, we ask patients to hold their ibrutinib for 3 days before and after minor procedures (tooth extractions, bunion surgery, etc.) and 7 days before and after for major surgeries ( gall bladder removal, knee surgery). Also, we do not start ibrutinib until all bleeding complications have resolved post-surgery. In some patients whose therapy is stopped even for brief periods of time, the lymph nodes can transiently increase. If the patient was responding before, it almost always happens that re-starting the drug will result in these nodes shrinking again. In general, this does not signify that patients are resistant to the drug. This flare effect generally does not occur when people have been on ibrutinib for a long time. For this reason, I generally recommend putting off elective surgery until 9-12 months after starting ibrutinib when possible.
How long does it take for ibrutinib to work?
For some a very good partial or clinical complete response can emerge clinically by 3-6 months.
What are the side effects of ibrutinib?
In general, the early side effects commonly seen with ibrutinib include fatigue, loose stools, heart burn, and rash. The loose stools associated with ibrutinib can often be treated with Imodium (loperamide) or Lomotil (diphenoxylate/atropine).
What is the most common progression of ibrutinib?
For early relapse, it is more common to see Richter’s transformation emerge as the most common type of progression on ibrutinib. Typically, this presents in the setting of most sites of disease showing tumor reduction whereas enlargement in 1-2 nodal areas is seen.
Does ibrutinib cause bruising?
Since starting ibrutinib, I have noticed that the bruising on my arms and legs have increased. Does this mean I am at a big risk for having major bleeding complications? Several studies comparing ibrutinib to other therapies have shown that there is a risk of minor bleeding complications such as bruising. In virtually all cases, this effect is not one that leads to debilitating or life-threatening bleeding. The bruising is often cosmetic and can occur in sensitive spots of the body, such as the face where no trauma has occurred. These spots are generally concealable by makeup and go away with time. The exception is, if surgery is required or other blood thinners are used, then continuing to take ibrutinib can increase the risk of serious bleeds. For blood thinners, the most dangerous one is Coumadin and most clinical trials performed with ibrutinib excluded patients taking this.
Can I take ibrutinib at any time of the day?
Identifying a single time during the day to take it is probably the most important thing to do. This will assure you take it at a set time every 24 hours which assures the best chance of it working.
What is the highest response to ibrutinib?
Response to ibrutinib is highest in patients with the MYD88 L265 mutation and wild-type CXCR4, less in patients with MYD88 L265P and the CXCR4 WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) mutation, and lowest in those with wild-type MYD88. Treon et al have reported major responses to ibrutinib in two patients in two patients with wild-type MYD88, on the basis of allele-specific polymerase chain reaction (AS-PCR) assays, in whom Sanger sequencing in tumor samples identified harbored MYD88 mutations that were not amenable to AS-PCR analysis for MYD88 L265P. [ 38]
What is the FDA approved drug for Waldenström macroglobulinemia?
In January 2015, ibrutinib (Imbruvica) became the first drug approved by the US Food and Drug Administration (FDA) for treatment of Waldenström macroglobulinemia. [ 35] Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor; it forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. The approval is based on results of a multicenter phase II study in which 63 patients with previously treated Waldenström macroglobulinemia demonstrated a response rate of 62% (very good partial responses of 11% and partial responses of 51%). These responses were maintained and the median duration of response (DOR) had not been reached, with a range of 2.8+ to 18.8+ months. [ 36]
Is ibrutinib a single agent?
Single-agent ibrutinib demonstrated high efficacy in an open-label substudy of the larger iNNOVATE trial. In 31 adults with WM that was refractory to rituximab and who had received a median of four previous therapy regimens, 90% of patients had an overall response, of which 71% were major responses, after a median follow-up of 18.1 months. The estimated 18-month progression-free survival rate was 86% (95% confidence interval [CI], 66-94%) and the estimated 18-month overall survival rate was 97% (95% CI, 79-100%). [ 7]
Is ibrutinib monotherapy safe?
A prospective study by Treon et al of ibrutinib as primary therapy in 30 symptomatic patients with untreated Waldenström macroglobulinemia found that ibrutinib monotherapy is highly active, produces durable responses, and is safe. In patients with wild-type CXCR4 versus those with mutated CXCR4, rates of major (94% vs 71%) and very good partial (31% vs 7%) responses were higher and time to major responses more rapid (1.8 vs 7.3 months; P = 0.01). [ 39]
Overview
Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic l…
Medical uses
Ibrutinib is used to treat chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia, and as a second-line treatment for mantle cell lymphoma, marginal zone lymphoma, and chronic graft vs host disease. BTK inhibition by ibrutinib impairs the BCR signalling pathway, which is a key dependency of malignant B cells, but it has been shown that BTK inhibition also interferes with CD40 signalling, B cell adhesion and migration.
Adverse effects
Very common (>10% frequency) adverse effects include pneumonia, upper respiratory tract infection, sinusitis, skin infection, low neutrophil count, low platelet counts, headache, bleeding, bruising, diarrhea, vomiting, inflammation of mouth and lips, nausea, constipation, rash, joint pain, muscle spasms, musculoskeletal pain, fever, and edema.
Common (1–10% frequency) adverse effects include sepsis, urinary tract infection, non-melanom…
Pharmacology
Ibrutinib oral bioavailability is 3.9% in a fasting state, 8.4% in a fed state, and 15.9% after consumption of grapefruit juice.
Ibrutinib is a potent, irreversible inhibitor of Bruton’s tyrosine kinase (BTK). It forms a covalent bond with the cysteine residue C481 in the BTK active site, leading to sustained inhibition of BTK enzymatic activity. BTK is an important signalling molecule of the B-cell antigen receptor (BCR) …
History
Ibrutinib was created by scientists at Celera Genomics as a tool compound for studying BTK function; it covalently binds its target which is ideal for a reagent but generally not considered ideal for drugs.
In 2006, in the course of acquiring an HDAC-focused program from Celera after its own initial discovery program had failed, Pharmacyclics also picked up Celera's small molecule BTK inhibito…
Cost
The typical cost of ibrutinib in the United States is about $148,000 a year. Preliminary PK/PD focused research found that people could potentially be put on lower and less expensive regimens of ibrutinib without losing efficiency; however, no data showing efficiency of lower doses has been published.
Janssen Pharmaceutica and Pharmacyclics introduced a new single dose tablet formulation with …
External links
• "Ibrutinib". Drug Information Portal. U.S. National Library of Medicine.
• Ibrutinib, National Cancer Institute Drug Dictionary