Systems controls are needed to reduce mistaken tests for hemophagocytic lymphohistiocytosis, results of a prospective quality-improvement cohort study.

ABSTRACT: Medical diagnosis and therapy often rely on laboratory testing. We observed mistaken testing in evaluations for hemophagocytic lymphohistiocytosis (HLH) that led to delays and adverse outcomes. Physicians were mistakenly ordering interleukin-2 and quantitative natural killer cell flow cytometry, rather than soluble interleukin 2 receptor (sIL2R) or qualitative natural killer functional tests in the evaluation of patients suspected to have HLH.We initiated a prospective quality improvement project to reduce mistaken testing, reduce delays in correct testing due to mistaken ordering, and improve HLH evaluations. This consisted of provider education, developing an evaluation algorithm, and ultimately required systems interventions such as pop-ups and removal of the mistaken tests from the electronic ordering catalog.Active education reduced mistaken testing significantly in HLH evaluations from baseline (73.3% vs 33.3%, P = .003, relative risk reduction (RRR) 54.5%), but failed to meet the pre-specified RRR cutoff for success (70%). Education alone did not significantly reduce the proportion of HLH evaluations with delays in sIL2R testing (23.3% vs 7.4%, P = .096). Mistaken testing increased after the active intervention ended (33.3% vs 43.5%, P = .390, with RRR 40.7% from baseline. Mistaken test removal was successful: mistaken testing dropped to 0% (P < .001, RRR 100%), saved $14,235 yearly, eliminated delays in sIL2R testing from mistaken testing (23.3% vs 0%, P = .008), and expedited sIL2R testing after admission for HLH symptoms (14.6 days vs 3.8 days, P = .0012). These data show systems controls are highly effective in quality improvement while education has moderate efficacy.

Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

INTRODUCTION: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. METHODS: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011-2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. RESULTS: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. CONCLUSIONS: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.