scholarly journals Zanubrutinib (Brukinsa)

2021 ◽  
Vol 1 (12) ◽  
Author(s):  
Reimbursement Team
Keyword(s):  
Tyrosine Kinase ◽  
International Workshop ◽  
Performance Status ◽  
Adult Patients ◽  
Prior Treatment ◽  
Consensus Panel ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor ◽  
Line Of Therapy ◽  
Public Drug

CADTH recommends that Brukinsa be reimbursed by public drug plans for the treatment of adult patients with relapsed or refractory Waldenström macroglobulinemia (WM), if certain conditions are met. Brukinsa should only be covered to treat patients with relapsed or refractory WM who have received at least 1 prior line of therapy, meet at least 1 criterion for treatment according to International Workshop on WM (IWWM) consensus panel criteria, and have good performance status. Patients eligible for reimbursement of Brukinsa should not have disease transformation, which is WM that has transformed into another type of cancer, or received prior treatment with a drug of the same class (i.e., a Bruton tyrosine kinase [BTK] inhibitor) unless such therapy was stopped because the drug was not tolerated and the disease had not progressed. Brukinsa should only be reimbursed if prescribed by a clinician with expertise and experience in the treatment of WM and monitoring of therapy and if it does not cost more than other treatments for WM.

scholarly journals Response of renal cell carcinoma to ibrutinib, a bruton tyrosine kinase inhibitor, in a patient treated for chronic lymphocytic leukemia

2017 ◽  
Vol 11 (5) ◽  
pp. 237 ◽  
Author(s):  
Gregory W. Hosier ◽  
Naji J. Touma
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor

Ibrutinib is a bruton tyrosine kinase (BTK) inhibitor approved for B cell malignancies. Although there are currently two clinical trials evaluating ibrutinib in combination with nivolumab (programmed cell death protein 1, PD-1, inhibitor) or everolimus (mammalian target of rapamycin, mTOR, inhibitor) for metastatic renal cell carcinoma (RCC), there are no reports of RCC (metastatic or non-metastatic) showing response to a BTK inhibitor in humans. Here we report a 22-month clinical response of biopsy-proven RCC to ibrutinib. This is unexpected, given that BTK is not wellimplicated in RCC pathophysiology. We explore a possible mechanism for the response of RCC to ibrutinib through inhibition of interleukin-2-inducible T-cell kinase (ITK) leading to enhanced antitumour immune responses.

A randomized phase 2 study of the Bruton tyrosine kinase (Btk) inhibitor acalabrutinib alone or with pembrolizumab for metastatic pancreatic cancer (mPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 4130-4130 ◽  
Author(s):  
Michael J. Overman ◽  
Charles D. Lopez ◽  
Al Bowen Benson ◽  
Sattva Swarup Neelapu ◽  
Niharika B. Mettu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tyrosine Kinase ◽  
Metastatic Pancreatic Cancer ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor ◽  
Randomized Phase 2

A randomized, multicenter, double-blind, placebo-controlled study of the Bruton tyrosine kinase inhibitor, ibrutinib, versus placebo in combination with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS483-TPS483 ◽  
Author(s):  
Margaret A. Tempero ◽  
Lisa M Coussens ◽  
Lawrence Fong ◽  
Robert Manges ◽  
Priyanka Singh ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Ductal Adenocarcinoma ◽  
Controlled Study ◽  
Leptomeningeal Disease ◽  
Karnofsky Performance Score ◽  
Line Treatment ◽  
Double Blind ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor

TPS483 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred regimen for front-line treatment. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) shows antitumor activity in preclinical PDAC models, in part, due to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia with simultaneous enhanced presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015). This randomized trial will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind RESOLVE trial (NCT02436668; PCYC-1137-CA) will compare ibr vs. placebo in combination with Nab-P/GCB in approximately 320 patients with untreated metastatic PDAC. Key eligibility criteria include histologically confirmed metastatic PDAC; stage IV diagnosis within 6 weeks of randomization; adequate hematologic, hepatic, and renal function; and Karnofsky performance score ≥ 70. Key exclusion criteria include prior therapies (chemotherapy for primary PDAC, BTK inhibitor, or radiotherapy), neuroendocrine or acinar pancreatic carcinoma, known brain or leptomeningeal disease, and history of stroke or intracranial hemorrhage < 6 months prior to enrollment. Patients will be randomized to oral ibr (560 mg) or matched placebo given daily in combination with Nab-P (125 mg/m2) and GCB (1,000 mg/m2) on days 1, 8, and 15 of a 28-day cycle until disease progression or treatment is no longer tolerated. A safety run-in phase will evaluate the ibr combination prior to the randomization portion of the study. The primary endpoint is progression-free survival; secondary endpoints include overall survival and safety. Enrollment in the trial has been initiated. Clinical trial information: NCT02436668.

scholarly journals Bruton Tyrosine Kinase Inhibition and Its Role as an Emerging Treatment in Pemphigus

2021 ◽  
Vol 8 ◽  
Author(s):  
Aikaterini Patsatsi ◽  
Dedee F. Murrell
Keyword(s):  
Tyrosine Kinase ◽  
Pemphigus Vulgaris ◽  
Lymphocytic Leukemia ◽  
Proof Of Concept ◽  
Phase 2 Trial ◽  
Mantle Cell ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor ◽  
New Treatment ◽  
Btk Inhibitors

Bruton Tyrosine Kinase (BTK) has a key role in multiple pathways involved in inflammation and autoimmunity. Therefore, BTK has become a new therapeutic target for a group of hematologic and autoimmune disorders. The pharmaceutical industry has invested in the clinical development of BTK inhibitors during the last decade. Ibrutinib, for example, which was the first BTK inhibitor to be used in clinical trials, has two approved indications, mantle cell lymphoma and chronic lymphocytic leukemia, and remains under evaluation for additional indications. Rillzabrutinib (PRN1008) is a new, highly potent and selective inhibitor of BTK. Early studies performed in canine pemphigus demonstrated effectiveness. A proof-of-concept, multicenter, phase 2 trial has recently showed the efficacy and safety of oral rilzabrutinib in pemphigus vulgaris. In this mini review, we present evidence regarding the mechanisms affected by BTK inhibition and the concept of BTK inhibition as an emerging new treatment in pemphigus.

scholarly journals Brexucabtagene Autoleucel (Tecartus)

2021 ◽  
Vol 1 (8) ◽  
Author(s):  
Reimbursement Team
Keyword(s):  
Health Status ◽  
Tyrosine Kinase ◽  
Mantle Cell Lymphoma ◽  
Systemic Therapy ◽  
Cell Lymphoma ◽  
Cellular Therapies ◽  
Mantle Cell ◽  
Btk Inhibitor ◽  
The Cost ◽  
Public Drug

CADTH recommends that Tecartus should be reimbursed by public drug plans for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL) after 2 or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor if certain conditions are met. Tecartus should only be reimbursed if prescribed as a one-time therapy by experienced specialists in centres delivering cellular therapies, and the cost of Tecartus is reduced. Tecartus should only be covered to treat patients with R/R MCL who have received treatment with a BTK inhibitor (ibrutinib or acalabrutinib) and are in a clinically reasonable health status to tolerate the treatment.

scholarly journals Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies

2021 ◽  
Vol 11 ◽  
Author(s):  
Hussein A. Abbas ◽  
William G. Wierda
Keyword(s):  
Adverse Events ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies ◽  
Bruton Tyrosine Kinase ◽  
Btk Inhibitor

Bruton tyrosine kinase (BTK) is a validated target for treatment of B-cell malignancies, and oral inhibitors of BTK have emerged as a standard of care for these diseases. Acalabrutinib is a second generation, highly selective, potent, covalent BTK inhibitor that exhibits minimal off-target activity in in vitro assays, providing the potential to improve tolerability over the first-in-class BTK inhibitor, ibrutinib. Acalabrutinib was approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) in the US in 2017 and 2019, respectively. Acalabrutinib is also undergoing trials for other B-cell malignancies, both as monotherapy and in combinations. In this review, we discuss results from clinical trials evaluating the efficacy and safety of acalabrutinib in patients with CLL, MCL, and Waldenstrom’s macroglobulinemia. Recent phase 3 data showed that acalabrutinib improved progression-free survival (PFS) compared with rituximab plus idelalisib or rituximab plus bendamustine in patients with relapsed/refractory CLL, and acalabrutinib with or without obinutuzumab improved PFS compared with chlorambucil plus obinutuzumab in patients with treatment-naïve CLL. Overall, acalabrutinib had a tolerable safety profile, with most adverse events being grade 1/2 severity (most commonly headache and diarrhea) and a low rate of discontinuation due to adverse events.

Combination of ACY1215, a Selective Histone Deacetylase 6 (HDAC6) Inhibitor with the Bruton Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Represents a Novel Therapeutic Strategy in Mantle Cell Lymphoma (MCL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1660-1660 ◽  
Author(s):  
Eva Sahakian ◽  
Jennifer Rock-Klotz ◽  
Bijal D. Shah ◽  
John Powers ◽  
Jennifer L. Cultrera ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Lines ◽  
Therapeutic Strategy ◽  
Dependent Manner ◽  
Apoptosis Induction ◽  
Antitumor Effects ◽  
Bruton Tyrosine Kinase ◽  
Hdac6 Inhibitor ◽  
Btk Inhibitor ◽  
Novel Therapeutic

Abstract Abstract 1660 Recently, we have found that HDAC6 is overexpressed in MCL cell lines and in primary human MCL cells. Knocking-down HDAC6 in MCL cells with a shRNA lentiviral system resulted in cell cycle arrest and apoptosis induction. Interestingly, MCL cells lacking HDAC6 displayed a significantly decreased STAT3 phosphorylation and abrogation of IL-10 gene transcriptional activity. ACY1215 is a novel, selective, orally bioavailable HDAC6 inhibitor. Treatment of MCL cell lines with this agent resulted in decreased cell viability and proliferation. In addition, ACY1215 inhibits IL-10 production in a dose dependent manner. Bruton tyrosine kinase (BTK) is a member of Tec family of kinases with a very distinct role in B-cell antigen receptor (BCR) signaling. The selective BTK-inhibitor PCI-32765 has shown promising pre-clinical and clinical activity in MCL. In addition to their direct anti-lymphoma effects, disruption of BTK also induces positive immunological changes such as inhibition of the immunosuppressive STAT3/IL-10 signaling pathway1. The above observations led us to determine whether the direct antitumor effects and the immunological properties of ACY1215 and PCI-32765 could be potentiated when these agents are used in combination. First, the viability of MCL cells was decreased when they were treated in vitro with either PCI-32765 or ACY1215. However, combination of these two agents resulted in a 3-fold increase in apoptosis induction, pointing to a synergistic effect of BTK and HDAC6 inhibition in MCL. The additional findings that this approach can increase the immunogenicity of MCL cells and anti-MCL immune responses has provided the proper framework for combining the selective HDAC6 inhibitor ACY1215 with BTK inhibition as a novel therapeutic strategy in MCL. Disclosures: Chen-Kiang: Bristol Myers Squibb: Consultancy; Pfizer: Research Funding. Jones:Acetylon Pharmaceuticals, Inc: Employment.

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