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PURPOSE: Ibrutinib is an irreversible Bruton's tyrosine kinase inhibitor that disrupts B-cell receptor signalling. It is licensed for treatment of low-grade B-cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma and lymphoplasmacytic lymphoma. A few case reports in the literature suggest that uveitis may be a side effect of ibrutinib treatment. A strong association between ibrutinib and uveitis is yet to be established in significant numbers. METHODS: The study is a retrospective case series, reporting cases of uveitis associated with ibrutinib from two tertiary centres in the United Kingdom: Liverpool University Hospitals NHS Foundation Trust and University Hospitals of Leicester NHS Trust. RESULTS: The study reports eight cases presenting over a four year period, with mean age of 66.8 years. Onset of uveitis was between 9 and 48 (median 14) months from commencing ibrutinib, categorising it as a Type D or delayed drug reaction. Cases included unilateral and bilateral; anterior, intermediate, posterior and panuveitis. There was an association with cystoid macular oedema or disc swelling. Severity varied from mild, to severe and vision threatening. Presenting visual acuity ranged from 6/9 to 6/60. In all eight cases, uveitis resolved after ibrutinib cessation. In two cases, reintroducing ibrutinib caused uveitis recurrence. CONCLUSION: Our case series provides evidence suggestive of a connection between ibrutinib and development of uveitis. Ibrutinib related uveitis appears to be more common than previously recognised. Ibrutinib cessation, if appropriate, appears to be the definitive management. Patients with ibrutinib-related uveitis benefit from multidisciplinary management involving communication between ophthalmologist and haemato-oncologist.
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Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK.
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Introduction: Rare cancers, in aggregate, represent a significant burden of disease in oncology and remain therapeutically challenging to manage due to a lack of clinical trials. Eccrine porocarcinoma is a rare cutaneous sweat-gland malignancy for which there remains no standard approach to metastatic disease. Case Presentation: We describe a patient diagnosed with metastatic disease, confirmed on bone biopsy; pathological analysis further revealed this was oestrogen receptor positive. She was commenced on the aromatase inhibitor letrozole, and denosumab, and showed a significant clinical and radiological response on bone scan within 7 months. At the time of report, over 2 years since commencing letrozole, she remains well with no evidence of progression. Conclusion: Our experience adds to the literature suggesting anti-oestrogen therapy can have significant benefit in patients with ER-positive non-breast cancer and is in keeping with increasing interest in therapies agnostic to site of origin but guided by expression/mutation of oncogenic drivers.