Case report: immune-mediated cerebellar ataxia secondary to anti-PD-L1 treatment for lung cancer.

Case presentation: A 66-year-old gentleman with metastatic non-small-cell lung cancer developed a wide-based gait following treatment on a clinical trial with cytotoxic chemotherapy and an anti-PD-L1 drug. He had no other significant past medical history of note. Brain imaging, blood tests and lumbar puncture did not reveal a structural, biochemical, paraneoplastic or infective cause. The main differential diagnoses were immune-mediated toxicity or a paraneoplastic syndrome. He was started on prednisolone on the suspicion that his symptoms represented an immune-mediated toxicity. His condition improved following this and his immunotherapy treatment was discontinued. Upon steroid withdrawal, his symptoms recurred and responded to further prednisolone. Conclusions: Immune-mediated toxicities can affect any part of the nervous system and should form part of the differential diagnosis for new neurological symptoms in a patient receiving immunotherapy. Corticosteroids should be the first-line treatment of immune-mediated toxicities. Immunotherapy should be permanently discontinued following severe toxicities.

Patient and treatment characteristics of emergency presentations due to immune-mediated toxicities.

BACKGROUND: The prevalence of immune-mediated toxicities from immune checkpoint inhibitors (ICIs) is well described. However, the characteristics and treatment patterns for patients with emergency presentations owing to immune-mediated toxicity are less well known. MATERIALS AND METHODS: This study reviews all emergency presentations in patients treated with ICI at a single centre between May 2018 and March 2020. The aims were to describe and quantify patient and treatment characteristics, toxicity type and outcomes. RESULTS: 1165 patients were treated with ICI, and there were 597 emergency presentations in 370 patients. Of these, 191/597 (32%) were owing to an immune-mediated toxicity, median age was 64 years, and 127/191 (67%) were men. The most common tumour types were melanoma (53%) and lung cancer (22%), and the most common ICI received was ipilimumab + nivolumab combination immunotherapy (42%), followed by pembrolizumab monotherapy (21%) and nivolumab monotherapy (20%). The median number of cycles received was three (range 1-54), and 75/191 (39%) had previous ≥ grade 2 immune-mediated toxicity. 29% patients required second-line immunosuppression. The median time in the hospital was four days. There was a rising number of emergency presentations reflecting overall increasing use of ICI. CONCLUSIONS: Over a quarter of patients treated with ICI had an emergency presentation, and immune-mediated toxicity accounted for 32% of these. A diagnosis of melanoma, treatment with combination immunotherapy and previous ≥ grade 2 immune-mediated toxicity were common in patients with immune-mediated toxicity. These data allow better identification of patients likely to require admission and forward planning for acute oncology services.

Exploring a Future for PI3K Inhibitors in Chronic Lymphocytic Leukemia.

PURPOSE OF REVIEW: Treatment for chronic lymphocytic leukemia has changed substantially in the past decade with an increasing shift towards use of targeted therapies, in particular agents targeting the B cell receptor pathway. Inhibition of PI3K, downstream of the B cell receptor pathway, represents an active therapeutic strategy in CLL. Here, we explore the relevance of PI3K inhibition in CLL, examine efficacy and toxicity of approved PI3K inhibitors in CLL, examine barriers to use of PI3K inhibitors, and explore strategies to optimize use of PI3K inhibitors in CLL. RECENT FINDINGS: Current generation PI3K inhibitors are active agents in CLL but their use may be limited by immune-mediated toxicities. Clinical trials of next generation PI3K inhibitors are ongoing and early data suggests these agents are highly active with potentially differentiated toxicity profiles. Furthermore, alternative dosing schedules may reduce toxicities of these agents. Inhibition of PI3K remains an important strategy in management of CLL and novel approaches to limit toxicities of PI3K inhibitors represent an important area of clinical research in CLL.