scholarly journals Cerebral Invasive Aspergillosis in a Case of Chronic Lymphocytic Leukemia with Bruton Tyrosine Kinase Inhibitor

2021 ◽  
Vol 28 (1) ◽  
pp. 837-841
Author(s):  
Omar Alkharabsheh ◽  
Alhareth Alsayed ◽  
Diana M. Morlote ◽  
Amitkumar Mehta

Bruton tyrosine kinase (BTK) inhibitors have become an important therapy for untreated and previously treated patients with chronic lymphocytic leukemia (CLL). Despite improved outcomes, rare adverse events, such as invasive fungal infections, have been reported with the use of first-generation BTK inhibitors. Invasive fungal infections carry a high morbidity and mortality risk. There have been several case reports describing the association between aspergillosis and ibrutinib treatment, but none with acalabrutinib, to our knowledge. In this case report, we describe a patient with CLL who developed an intracranial Aspergillus fumigatus infection while receiving acalabrutinib.

2016 ◽  
Vol 23 (14) ◽  
pp. 3734-3743 ◽  
Author(s):  
Viralkumar Patel ◽  
Kumudha Balakrishnan ◽  
Elena Bibikova ◽  
Mary Ayres ◽  
Michael J. Keating ◽  
...  

2021 ◽  
Vol 23 (2) ◽  
pp. 332-338
Author(s):  
Andrei A. Petrenko ◽  
Maria I. Kislova ◽  
Elena A. Dmitrieva ◽  
Eugene A. Nikitin

Chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically with the recently developed drugs targeting the B-cell receptor (BCR) signalling pathway. Acalabrutinib, a second generation Bruton tyrosine kinase inhibitor, was approved in 2020 in Russia for the treatment of patients with CLL. Acalabrutinib was developed as a more selective Bruton tyrosine kinase inhibitor then ibrutinib. This drug is aimed at reducing the adverse events that limit the use of ibrutinib, such as atrial fibrillation and bleeding. Phase I/II multicenter studies have demonstrated the efficacy and safety of acalabrutinib monotherapy in untreated CLL patients and in patients with relapsed/refractory CLL and ibrutinib intolerance. Phase III trials, ASCEND and ELEVATE-TN, compared acalabrutinib monotherapy and a combination of acalabrutinib and obinutuzumab versus standard therapies and demonstrated improved efficacy and tolerability of acalabrutinib. A phase III trial comparing acalabrutinib and ibrutinib monotherapy (ELEVATE-RR) is ongoing. The results of this study along with real-life clinical data could determine the place of acalabrutinib in CLL treatment.


2018 ◽  
Vol 226-227 ◽  
pp. 48
Author(s):  
Rashmi Kanagal-Shamanna ◽  
Preetesh Jain ◽  
Keyur Patel ◽  
Carlos Bueso-Ramos ◽  
Rajyalakshmi Luthra ◽  
...  

2020 ◽  
Vol 29 ◽  
pp. 096368972095020
Author(s):  
Sara Bravaccini ◽  
Giovanni Martinelli ◽  
Claudio Cerchione

Chronic lymphocytic leukemia (CLL), with an incidence rate between 4 and 6 cases per 100,000 persons per year, is considered the most prevalent leukemia in the western world. Chemoimmunotherapy (such as fludarabine, cyclophosphamide, and rituximab), bendamustine plus rituximab, and, more recently, novel agents such as ibrutinib (Bruton tyrosine kinase inhibitor), idelalisib (phosphatidylinositol-3-kinase δ inhibitor), and venetoclax (BCL-2 inhibitor) have changed the management of CLL. Shanafelt and colleagues compared the efficacy of ibrutinib–rituximab with that of standard chemoimmunotherapy in patients with treatment-naïve CLL. They did not, however, mention that the therapy varies on the basis of where patients live and, given that local guidelines not immediately reflect US Food and Drug Administration (FDA) updates, discrepancies in treatment occur. Important CLL goals are the availability of rapidly reproducible tests, standardization of national and international guidelines, and FDA approval-based treatment reimbursement.


2017 ◽  
Vol 103 (1_suppl) ◽  
pp. S37-S40 ◽  
Author(s):  
Elisa Albi ◽  
Stefano Baldoni ◽  
Patrizia Aureli ◽  
Erica Dorillo ◽  
Beatrice Del Papa ◽  
...  

Purpose Richter syndrome (RS) is a rare event in chronic lymphocytic leukemia (CLL) that is influenced by biological factors and prior CLL treatments. Ibrutinib is a Bruton tyrosine kinase inhibitor that has shown remarkable efficacy in CLL; however, little is known about its relationship to RS. We report a case of ibrutinib efficacy against CLL in a patient with prolonged remission of RS. Methods The patient was diagnosed with CLL in 2003. Biological findings at onset included absent ZAP70 expression, mutated IGVH, and NOTCH1 mutation. He was treated with FCR with partial response. In 2013, he progressed to RS, not clonally related to the underlying CLL. The patient was treated with anthracycline- and platinum-based regimens, obtaining a complete remission. After 3 years, he presented a CLL progression with worsening lymphocytosis, anemia, thrombocytopenia, increased splenomegaly, and lymphadenopathies. Positron emission tomography-computed tomography scan excluded pathologic uptake. Thus, he was started on ibrutinib. Results At 12 months’ follow-up, we observed white blood cell normalization, increased hemoglobin and platelet levels, disappearance of lymphadenopathy, and spleen size reduction. Therapy was well-tolerated with no evidence of RS. Conclusion This case demonstrates sustained RS remission in a patient with CLL under ibrutinib therapy, thus improving our knowledge on the use of this new drug in CLL and beyond.


2017 ◽  
Vol 11 (5) ◽  
pp. 237 ◽  
Author(s):  
Gregory W. Hosier ◽  
Naji J. Touma

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.


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