Imbruvica

INTRODUCTION: Two cases of late presentation (>5 years) of bilateral pseudophakic macula edema related to oral tyrosine kinase inhibitors are described. These cases are the first of their type in the published literature. A review of ocular inflammatory complications of tyrosine kinase inhibitors in the current literature is explored. CASE PRESENTATION: Case 1 is an 83-year-old female who has been stable on ibrutinib (Imbruvica® ) for chronic lymphocytic leukemia...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

WHAT IS THIS SUMMARY ABOUT?: This article provides a short summary of 5-year results from the iNNOVATE trial. The original paper was published in the Journal of Clinical Oncology in October 2021. People with Waldenström's macroglobulinemia (WM) were randomly divided into two groups of 75 people each. One group received a combination treatment composed of two drugs, ibrutinib plus rituximab, and the other group took placebo ("sugar pill") plus rituximab. Ibrutinib (also known by the brand name Imbruvica® ) is a drug that reduces cancer cells' ability to multiply and survive...

Ibrutinib (Imbruvica) has received a new indication for the treatment of graft-versus-host disease in pediatric patients at least one year of age when one or more systemic therapies have failed.The product's labeling warns of the risk of hemorrhage, infections, cardiac arrythmias, cardiac failure and sudden death, hypertension, cytopenia, secondary primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity.The most common adverse effects include laboratory abnormalities, musculoskeletal pain, pyrexia, pneumonia, abdominal pain, stomatitis, diarrhea, and headache...

Ibrutinib (IMBRUVICA® ), a small molecule inhibitor of Bruton's tyrosine kinase (BTK) developed by Pharmacyclics, Inc. and Janssen Pharmaceutical, is well established as a treatment for B-cell malignancies and is also approved in the USA in adult patients with chronic graft-versus-host disease (cGVHD) and in Japan in adults and adolescents aged ≥ 12 years with cGVHD. Ibrutinib was approved in August 2022 in the USA for use in pediatric patients with cGVHD after failure of one or more lines of systemic therapy and is the first treatment approved for use in this group of patients aged < 12 years (ibrutinib is now indicated for the treatment of adult and pediatric patients aged 1 year and older with cGVHD after failure of one or more lines of systemic therapy)...

Allogeneic hematopoietic stem cell transplant (alloHSCT) can be a life-saving treatment for patients with hematological disorders but far too often carries the feared complication of graft-versus-host disease (GVHD). The first-line treatment of GVHD is typically corticosteroids, but steroid-refractory chronic GVHD (cGVHD) has led to the Food and Drug Administration (FDA) approval of ruxolitinib (Jakafi), ibrutinib (Imbruvica), and belumosudil (Rezurock). Patient 1 was a four-year-old female diagnosed with natural killer (NK) cell dysfunction who underwent alloHSCT with cells from a 9/10 National Marrow Donor Program (NMDP) donor and subsequently developed chronic GVHD (cGVHD) of the skin and gut...

BACKGROUND: The "accelerated" chronic lymphocytic leukemia (aCLL) is a relatively rare form of CLL progression. The expanded proliferation centers in aCLL have been associated with adverse prognostic features and propensity to more aggressive behavior with shorter survival. CASE: An atypical case of aCLL with distinct features is described. A 66-year-old female presented with a marrow replacing process associated with multiple osseous metastases and trivial lymphadenopathy...

Ibrutinib (Imbruvica; PCI-32765) is an orally administered inhibitor of Bruton's tyrosine kinase that has transformed the treatment of B-cell malignancies. However, ibrutinib has very low oral bioavailability that contributes to significant variability in systemic exposure between patients, and this has the potential to affect both efficacy and toxicity. We hypothesized that the oral bioavailability of ibrutinib is limited by CYP3A isoform-mediated metabolism, and that this pathway can be inhibited to improve the pharmacokinetic properties of ibrutinib...

Ibrutinib (Imbruvica®, 2013) is a Bruton's tyrosine kinase (BTK) inhibitor approved for multiple B-cell malignancies and cGVHD. Its treatment is associated with increased risk of cardiac adverse events. Atrial fibrillation is a common cause of therapy discontinuation and interruptions, which have been correlated with shorter progression-free survival in chronic lymphocyte leukemia (CLL) patients. Recently, Xiao et al. identified that ibrutinib-mediated atrial fibrillation is likely due to off-target CSK inhibition...

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system, caused by reactivation of John Cunningham polyomavirus, affecting mainly patients in an immunocompromised state. Recently, drug-associated PML is gaining attention as more cases of PML in connection with the use of various immunomodulatory drugs emerge. Over the last couple of years, sporadic reports have occurred about a possible association between PML and the use of a new immunomodulatory drug, ibrutinib (Imbruvica), primarily indicated for the treatment of various B-cell malignancies...

PURPOSE: On August 2, 2017, the Food and Drug Administration approved ibrutinib (IMBRUVICA) for the treatment of patients with chronic graft versus host disease (cGVHD) after the failure of one or more lines of systemic therapy. The approval was based on results from a single-arm, multicenter trial that enrolled patients with refractory cGVHD. This paper describes the FDA review of patient-reported outcomes (PRO) data from Study PCYC-1129-CA and the decision to incorporate descriptive PRO data in the FDA label to support the primary clinician-reported outcome results...

Ibrutinib (Imbruvica), an oral tyrosine kinase inhibitor (TKI) approved for treatment of B-cell malignancies, irreversibly inhibits the Bruton's tyrosine kinase (BTK). Its abundant metabolite, dihydrodiol-ibrutinib (ibrutinib-DiOH), which is primarily formed by CYP3A, has a 10-fold reduced BTK inhibitory activity. Using in vitro transport assays and genetically modified mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 and the multidrug-metabolizing CYP3A enzyme family can affect the oral bioavailability and tissue disposition of ibrutinib and ibrutinib-DiOH...

No abstract text is available yet for this article.

Single-agent ibrutinib is an effective therapy for three types of non-Hodgkin lymphoma: chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma, both in relapsed and refractory cases and as a frontline treatment; relapsed and refractory mantle cell lymphoma; and Waldenstrom's macroglobulinaemia in patients who have been treated previously with a different medication. This novel agent has changed the landscape for the aforementioned three subtypes of lymphoma therapies as an oral alternative to traditional chemoimmunotherapy...

(S)-N-Boc-3-hydroxypiperidine (S-NBHP) is a critical chiral intermediate in the synthesis of pharmaceuticals, including ibrutinib, the active pharmaceutical ingredient of the new drug Imbruvica approved for the treatment of lymphoma. An (R)-specific carbonyl reductase from Candida parapsilosis (CprCR, also known as R-specific alcohol dehydrogenase) that catalyzes asymmetric reduction to produce (S)-N-Boc-3-hydroxypiperidine (S-NBHP) was identified for the first time. When co-expressed with a glucose dehydrogenase from Bacillus megaterium in Escherichia coli Rosetta (DE3), recombinant crude enzyme exhibited an activity of 9 U/mg with N-Boc-3-piperidone as the substrate and 12 U/mg with glucose as the substrate...

Ibrutinib (Imbruvica® ) is an oral irreversible inhibitor of Bruton's tyrosine kinase, a B-cell receptor (BCR) signalling kinase expressed by various haematopoietic cells, B-cell lymphomas and leukaemias. The drug is indicated for the treatment of certain haematological malignancies, including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), which are the focus of this review. In phase III CLL/SLL trials, ibrutinib monotherapy was more effective than chlorambucil in the first-line treatment of elderly patients (RESONATE-2) and more effective than ofatumumab in previously-treated adults (RESONATE)...

(S)-N-Boc-3-hydroxypiperidine ((S)-NBHP) is a key pharmaceutical intermediate and the chiral source in synthesizing Imbruvica, which is a newly approved drug in lymphoma therapy by targeting Bruton's tyrosine kinase (BTK). Current chemical synthesis of (S)-NBHP suffered from the need of noble metal catalyst and low yield. The single reported bioconversion of (S)-NBHP was achieved by using recombinant ketoreductase, but enzyme sequence was kept confidential and the catalytic process suffered from the thermodeactivation and substrate inhibition...

No abstract text is available yet for this article.

Ibrutinib (Imbruvica; Pharmacyclics) is the first Food and Drug Administration-approved inhibitor of Burton's tyrosine kinase (BTK). Attenuation of BTK signaling ultimately leads to inhibition of B-cell proliferation and apoptosis. After a series of clinical trials, the Food and Drug Administration approved ibrutinib in patients with relapsed chronic lymphocytic leukemia in 2014 and Waldenström's macroglobulinemia in 2015. Those trials included rare grade 3+ hemorrhagic events associated with ibrutinib. Herein, we report a unique presentation of back pain due to iliopsoas muscle hemorrhage in a patient with Waldenström's macroglobulinemia after initiation of ibrutinib...