Acute gout flare of bilateral first metatarsophalangeal joints due to ibrutinib use in chronic lymphocytic leukemia

2021 ◽  
pp. 107815522110297
Author(s):  
Jaspreet Kaur ◽  
Shahaf Tuler ◽  
Constantin A Dasanu

Introduction Bruton tyrosine kinase inhibitors represent important tools in the therapeutic armamentarium against chronic lymphocytic leukemia (CLL) and other B-lymphoproliferative disorders. Case Report We describe herein a unique 65-year-old patient who presented with bilateral foot pain four months after starting treatment with ibrutinib for CLL. Of note, the patient had previously been diagnosed with gout, and was taking allopurinol prophylactically at the time of the event. Compliance with allopurinol was in excess of 99%. Yet, he was diagnosed with acute gout flare of bilateral first metatarsophalangeal (MTP) joints. Management & Outcome: Ibrutinib dose was reduced by one third, and the patient’s gout flare up was treated with ibuprofen as needed. After symptoms abated, ibrutinib was continued at 2/3rds of the dose, with an excellent CLL control. The patient tolerated this dose without any further adverse effects. Discussion/Conclusions: We have reported a unique side effect of acute bilateral first MTP joint gout flare likely triggered by ibrutinib use for CLL while the patient was taking a xanthine oxidase inhibitor. The mechanism by which ibrutinib caused this phenomenon remains to be elucidated.

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 33-40
Author(s):  
Carol Moreno

Abstract Despite the effectiveness of chemoimmunotherapy (CIT), in most cases the clinical course of chronic lymphocytic leukemia (CLL) is characterized by consecutive episodes of disease progression and need for therapy. Treatment possibilities for patients with CLL in whom CIT fails whose disease progresses after initial CIT include pathway inhibitors (PIs) and, for selected patients, cellular therapy (ie, allogeneic stem cell transplant, chimeric antigen receptor T cells). PIs (ie, Bruton tyrosine kinase inhibitors, phosphatidylinositol 3-kinase inhibitors, and BCL2 inhibitors) are revolutionizing the treatment of CLL. PIs have proved to be more effective than CIT, both as upfront therapy and for relapsed/refractory disease, largely because they may overcome the negative impact of adverse biomarkers (eg, TP53 aberrations, unmutated IGHV) on outcomes and because of their acceptable toxicity. In this article, the management of patients with relapsed/refractory CLL is discussed, with a particular emphasis on the role of PIs.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19509-e19509
Author(s):  
Mohammad Ammad Ud Din ◽  
Saad Jamshed

e19509 Background: It is unclear whether Bruton tyrosine kinase inhibitors (BTKi) contribute to the humoral dysfunction in chronic lymphocytic leukemia. Methods: A literature search of PubMed, EmCare, and Google Scholar was performed on December 5, 2020. Five studies met inclusion criteria out of 249 studies per PRISMA guidelines (n = 244). Results: Pleyer et al. and Zent et al. showed an adequate recall humoral response to the shingle vaccine (41.5% and 75% seroconversion rate respectively), however, de novo response to hepatitis B vaccine was greatly reduced. Conflicting results were seen for the influenza vaccine as Sun et al. showed a significant increase in post-vaccination geometric mean titers for all three strains while only 7% of patients demonstrated seroconversion in the study by Douglas et al. None of the patients responded to the pneumococcal conjugate vaccine in a study by Andrick et al, though the results were not statistically significant (p = 0.029) (Table). Conclusions: Treatment with BTKi may not cause significant detrimental response to immunization but further studies are needed to elucidate longterm effects especially in patients with prior exposure to anti-CD20 antibodies.[Table: see text]


Author(s):  
Ross Salvaris ◽  
Stephen Opat

In the last decade, the treatment of chronic lymphocytic leukemia (CLL) has shifted away from chemoimmunotherapy toward targeted novel agents such as small molecule inhibitors and antibodies. Here, we give an overview of the pharmacology of venetoclax and obinutuzumab and the evidence from early phase to Phase III trials that have shaped how they are used in the treatment of CLL. Venetoclax, an oral anti-apoptotic BCL-2 inhibitor, in combination with a CD20 antibody has shown superiority to chemoimmunotherapy in treatment-naive and relapsed/refractory CLL. Obinutuzumab is a novel anti-CD20 monoclonal antibody that has been safely combined with novel agents including venetoclax and Bruton tyrosine kinase inhibitors and has shown superiority over rituximab when combined with chlorambucil.


2020 ◽  
Vol 21 (4) ◽  
pp. 45-47
Author(s):  
Irina V. Poddubnaya ◽  
Tatyana E. Bialik ◽  
Natalya N. Glonina ◽  
Olga B. Kalashnikova ◽  
Kamil D. Kaplanov ◽  
...  

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, with incidence rate of 4: 100 thousand per year, according to European data. CLL remains an incurable disease, with most patients over 60 years old. Immunochemotherapy schemes today remain the standard treatment approach for CLL. The advent of novel molecules expands possibilities of treating this disease. Targeted therapy with small molecule inhibitors of Bruton tyrosine kinase (BTK) occupies an important place in the treatment of patients with CLL, both for first-line therapy and for treatment of relapses. The drug acalabrutinib as a highly selective new generation of BTK inhibitor can be considered as an efficient and safe option for first-line therapy and for treatment of the disease relapse in patients with CLL, especially in patients with comorbidity, including cardiovascular diseases (CDV) or risk factors for CVD.


2021 ◽  
Vol 2021 (9) ◽  
Author(s):  
Jacob Schmelz ◽  
Philip Heesen ◽  
Anish Patnaik ◽  
Travis Holder ◽  
Hun J Lee ◽  
...  

2018 ◽  
Vol 25 (4) ◽  
pp. 1003-1005 ◽  
Author(s):  
Constantin A Dasanu

Although newer targeted agents improve survival in cancer patients, they have also been linked with unusual side effects. The most common side effects of Bruton tyrosine kinase inhibitors include fatigue, nausea, diarrhea, bruising, and cytopenias. We describe herein a case of an unusually severe articular syndrome with the use of ibrutinib in a patient with 17 p minus chronic lymphocytic leukemia. The severity of this side effect led to permanent discontinuation of this agent. As the causality ibrutinib-arthralgia seems legitimate, we expect further similar cases to surface in patients treated with Bruton tyrosine kinase inhibitors.


2022 ◽  
Vol 11 ◽  
Author(s):  
Florence Nguyen-Khac

Although the 17p deletion [del(17p)] is rare in cases of treatment-naive chronic lymphocytic leukemia (CLL), its frequency is higher in refractory/relapsed CLL – particularly in patients undergoing chemo(immuno)therapy. TP53 disruption (deletion and/or mutation) is the strongest prognostic factor for refractoriness to chemotherapy; the use of Bruton tyrosine kinase inhibitors and BCL2 inhibitors is then indicated. Rare cases of CLL can also harbor translocation or gain of the MYC oncogene. “Double-hit CLL” (with del(17p) and MYC gain) is associated with a very poor prognosis. The prognostic impact of TP53 disruption with MYC aberrations in patients receiving targeted therapies must now be evaluated.


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