Case series of unique adverse events related to the use of ibrutinib in patients with B-cell malignancies—A single institution experience and a review of literature

Shaikh, Hira; Khattab, Ahmed; Faisal, Muhammad Salman; Chilkulwar, Abhishek; Albrethsen, Mary; Sadashiv, Santhosh; Fazal, Salman

doi:10.1177/1078155218788707

Cited by 11 publications

(7 citation statements)

References 18 publications

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“… 19 , 20 These include early autoimmune skin lesions, palindromic rheumatoid arthritis, bullous pemphigoid, autoimmune haemolytic anaemia, autoimmune cytopenia, severe arthritic syndrome and autoimmune myelitis. 21 , 22 These, like the presented cases, have been found to be responsive to steroids. 21 , 23 Autoimmune phenomena have been postulated to be related to ibrutinib's inhibition of interleukin-2-inducible T-cell kinase, thereby causing a Th1 shift and a pro-inflammatory response of Th1 cells.…”

Section: Discussionsupporting

confidence: 69%

Ibrutinib-related uveitis: A case series

Chiu

Goh

Ling

et al. 2022

American Journal of Ophthalmology Case Reports

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Purpose Four cases of ibrutinib-related uveitis are presented, which are to the best of our knowledge the first in the literature. Possible mechanisms of ibrutinib-mediated uveitis are explored. Observations Case 1 is a 60-year-old female who had been stable on 1 year of ibrutinib for chronic lymphocytic leukaemia. She was diagnosed with ibrutinib-related uveitis, which responded well to topical steroids. Case 2 is a 63-year-old male diagnosed with uveitis after 2 years of ibrutinib treatment for chronic lymphocytic leukaemia. He responded well to topical and oral steroids; however, he continued to have uveitis relapses after weaning steroids. Case 3 is a 69-year-old male diagnosed with uveitis after 18 months of ibrutinib treatment. He was trialed on topical and intravenous steroids, and restarted ibrutinib without worsening of symptoms. Case 4 is a 66-year-old female who developed uveitis after being stable on ibrutinib for 3 years. She responded well to topical steroids. Conclusions and Importance Inflammatory complications of tyrosine kinase inhibitors are well described. While ibrutinib, and other kinase inhibitors, are generally well-tolerated, there are increasing reports of ocular toxicities, including uveitis. It is recommended to monitor patients for potential ocular adverse effects and facilitate rapid ophthalmologic assessment.

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Section: Discussionsupporting

confidence: 69%

Ibrutinib-related uveitis: A case series

Chiu

Goh

Ling

et al. 2022

American Journal of Ophthalmology Case Reports

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“…Intermittent cessation of ibrutinib was reported to provide neurological improvement. 10 The current case had a distinct entity with the development of PNP only, which was directly associated with the agent rather than with any cerebrovascular event. The treatment was discontinued when grade 3 polyneuropathy was detected and the patient's complaints completely regressed.…”

Section: Discussionmentioning

confidence: 72%

“…A recent case report series by Shaikh et al reported single adverse events such as palindromic rheumatoid arthritis, diffuse spongiotic dermatitis, bullous pemphigoid, recurrent hemorrhage, stroke, recurrent paronychia, intramedullary fibrosis, recurrent joint pains, pulmonary aspergillosis and autoimmune hemolytic anemia. 10 Mato et al recently reported four cases of pneumonitis associated with ibrutinib. 11 Cataracts were reported in 3% of the patients in a review by Byrd et al, and in the same study, tumor lysis syndrome, which is a very rare adverse event, was also reported.…”

Section: Discussionmentioning

confidence: 99%

Ibrutinib-induced polyneuropathy: A case report

Cömert

Albayrak

Yıldız

et al. 2020

J Oncol Pharm Pract

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Introduction Ibrutinib is an oral irreversible inhibitor of Bruton’s tyrosine kinase signaling. It is a well-tolerated agent with some side-effects, the most common of which are atrial fibrillation, diarrhea, upper respiratory tract infection, fatigue, nausea, rash and cytopenias. Most of these toxicities are mild, although some have a severe clinical course. Case report The case is here reported of a chronic lymphocytic leukemia patient with ibrutinib-induced polyneuropathy. A 63-year-old male patient with chronic lymphocytic leukemia was given ibrutinib as a third line treatment regimen. After the 10th month of therapy he had progressive complaints of numbness and tingling in his legs. The patient was diagnosed as grade 3 sensorineural polyneuropathy with electromyography. Management and outcome: Considering that ibrutinib treatment may cause neuropathy, the ibrutinib was discontinued, after which the neuropathic complaints improved. However, the neck and axillary lymph nodes were enlarged and treatment had to be re-started therefore ibrutinib was started at a low dose and gradually increased. The patient is currently in the 14th month of treatment and still using ibrutinib without any severe side-effects. Discussion To the best of our knowledge, polyneuropathy as a unique side-effect of ibrutinib has not been previously reported. In addition to the well-known side effects of ibrutinib treatment, it should be kept in mind that polyneuropathy may also develop.

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“…Other inflammatory reactions include lobular/septal panniculitis (21%) and rare reported cases of Sweet syndrome, pyogenic granuloma, pyoderma gangrenosum, granulomatous dermatitis, SJS, bullous pemphigoid, exfoliative toxin-positive staphylococcal scalded skin syndrome, and cutaneous lymphoid hyperplasia or cutaneous pseudolymphoma (CPL). 294,295,[300][301][302][303][304][305][306][307][308][309][310] Finally, secondary BCCs and cutaneous SCCs are seen in up to 4% of patients treated with ibrutinib. 299,311 Table 1 lists in detail the types of dermatologic toxicities associated with BTK inhibitors.…”

Section: Btk Inhibitorsmentioning

confidence: 99%

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

et al. 2021

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Background: Advances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small-molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities. Methods: We conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) mitogen-activated protein kinase; (b) growth factor/multi-tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta-analyses, and case reviews/reports were included for analysis.Results: Dermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life-threatening adverse skin reactions.Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs.Squamous cell carcinoma with keratoacanthoma-like features was associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs.Conclusions: Dermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of "oncodermatology/dermatopathology."

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Case series of unique adverse events related to the use of ibrutinib in patients with B-cell malignancies—A single institution experience and a review of literature

Cited by 11 publications

References 18 publications

Ibrutinib-related uveitis: A case series

Ibrutinib-related uveitis: A case series

Ibrutinib-induced polyneuropathy: A case report

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

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