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.

No abstract

Background Despite high effectiveness of therapeutic plasma exchange as the first‐line therapy, thrombotic thrombocytopenic purpura (TTP) remains a life‐threatening condition and may require utilization of adjunct modalities in certain patients. Mortality In TTP Score (MITS) is a prognostic risk stratified scoring tool designed to predict mortality in hospitalized patients with TTP. There has not been an external validation of MITS to date. Study Design and Methods We performed an external validation of MITS in patients hospitalized with TTP using the National Inpatient Sample database from 2016 to 2019. We identified 4589 patients who met the selection criteria. Univariate and multivariable logistic regression models were run based on the MITS parameters of arterial thrombosis, intracranial haemorrhage, age, renal failure, ischemic stroke, platelet transfusion, and myocardial infarction to evaluate prognostic performance and discriminatory power of this tool. Results All‐cause mortality was reported more frequently in female subjects (57.8%), Caucasian race (58.9%), and ages 60 years, and above (52.3%). In a multivariable analysis, the variables included in the MITS criteria remained significant predictors of mortality. Moreover, MITS correlated with mortality risk. Our model's area under the receiving operator character curve was 71%, compared to 78.6% in the derivation cohort study. Discussion In this external validation cohort, performance of MITS was similar to the derivation cohort, validating it as a valuable clinical tool that may guide management of TTP patients.

No abstract

e16232 Background: The addition of immunotherapy in neoadjuvant hepatocellular carcinoma (HCC) has been studied recently in early phase clinical trials due to high rate of recurrence after surgery. We aim to systematically review the evidence of efficacy and safety of neoadjuvant immunotherapy treatment. Methods: We carried out a systematic search on MEDLINE, Cochrane, and ASCO meetings library. Screening was done to include clinical trials with HCC patients who underwent any combination of neoadjuvant immune checkpoint inhibitors (ICIs). Quality assessment was performed using methodological index for non-randomized studies (MINORS) tool. The primary efficacy outcomes evaluated included complete pathological response (pCR), major pathological response (MPR), 1 year recurrence free survival (RFS) and overall response rate (ORR). Treatment related adverse events (TRAE) were assessed as a safety outcome. Predefined subgroup analysis was performed based on studies including of tyrosine kinase inhibitors (TKIs) in regimen. Data was analyzed using R version 4.2.1. Results: 5 phase I/II clinical trials were included consisting of 96 patients. Trials administered neoadjuvant immunotherapy agents nivolumab (with TKI cabozantinib) (N = 1), camrelizumab (with TKI apatinib) (N = 1), cemiplimab (N = 1) and nivolumab plus ipilimumab (N = 2). 78(81.2%) of patients were males. 56(59.3%) of patients had viral etiology. 14(14.5%) patients had surgeries delayed or cancelled due to any cause per trial protocols. Meta-analysis of 96 patients from 5 trials showed a pooled pCR rate of 14.49% (95% CI: 6.82 to 23.93%) with low heterogeneity (I2 = 0%, p value 0.55). Pooling the MPR resulted in an estimate of 35.30% (95% CI: 18.80% to 53.57%) with significant heterogeneity (I2 = 58.8%, p value 0.04). Three trials with total 45 patients reported a 12-month RFS rate of 51.08% (95% CI: 40.59 to 70.67%) with significant heterogeneity (I2 = 84.2%, p value 0.002). The overall response rate was 13.7% (95% CI: 6.9 to 22.1%) (I2 =0%, p =0.8). Overall rate of TRAE of any grade was 73.8% (95% CI: 63.1 to 82.5%) (I2 = 83.4%, p <0.001) among all trials and grade 3 adverse events was 21.21% (95% CI: 11.4 to 32.7%) (I2 = 33.8%, p = 0.159). 17(17.8%) patients had elevation in liver enzymes. On subgroup analyses, no difference in pathological outcomes, ORR and grade 3 adverse events was observed with addition of TKIs. Exploratory analysis showed no difference in pCR rates with single ICI vs combination with ipilimumab. Conclusions: The addition of ICIs in neoadjuvant settings appears to be a safe and feasible option. The addition of TKIs to neoadjuvant ICIs does not appear to affect pathological and safety outcomes. Further studies are needed to identify ICI based regimens to improve pCR rates and validate pathological outcomes in HCC after correlating with recurrence and survival.