Hemophagocytic Lymphohistiocytosis Secondary to Immune Checkpoint Inhibitor Therapy.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal systemic inflammatory syndrome. HLH has been reported as a rare immune-related adverse event (irAE) in patients receiving immunotherapy with nivolumab, ipilimumab, and/or pembrolizumab. The data are limited to case reports and case series. The objective of this research is to compile data on this rare but potentially life-threatening adverse event of immune checkpoint inhibitors (ICIs) and identify the common agents that cause this irAE, clinical spectrum, and successful management strategies to assist the treating oncologists. A review was done using PubMed database. Eligible articles included case reports and case series published from January 1, 2015, through February 1, 2021. Reports published in languages other than English were excluded. Data were compiled into a detailed supplementary table and simple descriptive analysis was used to interpret data. A total of 22 cases were included, which constituted 14 individual case reports and two case series. The immunotherapy prescribed consisted of antibodies against and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) in all 22 patients. Out of them, immunotherapy consisting of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies was prescribed in nine patients. Fever was the most common symptom at the presentation (90.9%). The most common laboratory findings were anemia (90.9%), thrombocytopenia (90.9%), and elevated ferritin (90.9%). All the patients received steroids (100%). HLH responded to treatment in 19 patients. Three patients died. Three patients were rechallenged with immunotherapy, with no recurrence of HLH. HLH in the setting of ICI therapy is life-threatening, but potentially treatable with early detection. However, diagnosis is often delayed due to difficulty in differentiating the presenting symptoms and laboratory findings from complications of cancer and other therapies. Majority have shown an adequate response to standard HLH treatment; however, some required a longer course of corticosteroids. HLH is not always associated with other irAE. Rechallenging with immunotherapy was successful in some patients after completing treatment for HLH.

Immunotherapy-induced pneumonitis in non-small cell lung cancer patients: current concern in treatment with immune-check-point inhibitors.

Purpose Immune-related adverse events (IrAEs) are auto-immune reactions associated with immune checkpoint inhibitor-based therapy (ICI). To date, little is known about immunotherapy-induced pneumonitis (IIP). In this study, we investigated the clinical and CT features of IIP in non-small cell lung cancer (NSCLC) patients treated with ICI. Methods CT images and clinical data of 98 NSCLC patients in our hospital were retrospectively analyzed after ICI therapy, and the incidence, onset time, CT findings, grade, treatment and prognosis of IIP were recorded. Results Nineteen patients developed IIP, which occurred 42∼210 days after ICI therapy, and the median time was 97 days. The CT findings for IIP showed multifocal ground-glass opacity (GGO) in 5 cases, patchy shadows in 6 cases, mixed distribution of patchy and strip-like shadows in 4 cases, and patchy shadows with honeycomb lung in 4 cases. The mean age and proportions of smokers, CD3+ and CD4+ of T lymphocyte subset in patients with IIP were significantly higher than those in patients without IIP (all p < 0.05). Among 19 patients with IIP, there were 10 patients with grade 1 ~ 2 and 9 patients with grade 3 ~ 4; 13 patients received hormone therapy, 12 of them were improved or stable, and 1 patient got worse after hormone therapy. No deaths from IIP were found. Conclusion IIP is a relatively rare but serious adverse event, and it is sensitive to hormone therapy. Its CT manifestations are diverse, and timely detection and treatment are the keys to reduce IIP.