Key Clinical MessageDrug‐induced aHUS is rare; however, early diagnosis is vital to reduce morbidity and mortality. With confirmation of the diagnosis, eculizumab appears to be a viable treatment option to suppress the pro‐inflammatory surge. Furthermore, adverse side effects of medications such as carfilzomib and gemcitabine should be considered in the appropriate settings.

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.

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Background Ibrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flutter). It is known that patients with cardiovascular disease (CVD) are at an increased risk for developing atrial arrhythmia. However, the rate of atrial arrhythmia in patients with pre-existing CVD treated with ibrutinib is unknown. Objective This study examined whether patients with pre-existing CVD are at a higher risk for developing atrial arrhythmias compared to those without prior CVD. Methods A single-institution retrospective chart review of patients with no prior history of atrial arrhythmia treated with ibrutinib from 2012 to 2020 was performed. Patients were grouped into two cohorts: those with CVD (known history of coronary artery disease, heart failure, pulmonary hypertension, at least moderate valvular heart disease, or device implantation) and those without CVD. The primary outcome was incidence of atrial arrhythmia, and the secondary outcomes were all-cause mortality, risk of bleeding, and discontinuation of ibrutinib. The predictors of atrial arrhythmia (namely atrial fibrillation) were assessed using logistic regression. A Cox-Proportional Hazard model was created for mortality. Results Patients were followed for a median of 1.1 years. Among 217 patients treated with ibrutinib, the rate of new-onset atrial arrhythmia was nearly threefold higher in the cohort with CVD compared to the cohort without CVD (17% vs 7%, p = 0.02). Patients with CVD also demonstrated increased adjusted all-cause mortality (OR 1.9, 95% CI 1.06-3.41, p = 0.01) and decreased survival probability (43% vs 54%, p = 0.04) compared to those without CVD over the follow-up period. There were no differences in risk of bleeding or discontinuation between the two cohorts. Conclusions Pre-existing cardiovascular disease was associated with significantly higher rates of atrial arrhythmia and mortality in patients with hematological malignancies managed with ibrutinib.

Objectives: To determine whether minor alterations in adrenal gland morphology at baseline CT in three common cancers indicate early metastasis. Methods: 689 patients (237 with lung cancer, 228 with breast cancer, 224 with melanoma) underwent baseline and follow-up CTs that included the adrenals. Two readers independently scored each adrenal at baseline CT as normal, smoothly enlarged, nodular or mass-containing. Adrenals containing a mass .10 mm were excluded. The appearance of each adrenal on the latest available CT was assessed for change since baseline. Cox models were used to assess the association between adrenal morphology at initial CT and subsequent development of adrenal metastasis (defined as new mass .10 mm, corroborated by follow-up imaging). k statistics were calculated to assess inter-reader agreement. Results: Initial and follow-up CT evaluations were recorded for 1317 adrenals (median follow-up, 18.6 months). At initial CT, Readers 1 and 2 interpreted 1242 and 1230 adrenals as normal, 40 and 57 as smoothly enlarged, 29 and 25 as nodular, and 6 and 5 as containing masses #10 mm, respectively. k-values were 0.52 (moderate) at initial CT and 0.70 (substantial) at follow-up. The hazard ratio for developing a metastasis at follow-up CT given an abnormal adrenal assessment at baseline was 0.7 [95% confidence interval (CI) 0.2-2.1; p50.47] for Reader 1, and 2.0 (95% CI 0.8-4.7; p50.12) for Reader 2. Conclusion: Minor morphological abnormalities of adrenals at initial CT did not represent early adrenal metastasis in most patients in this population. The adrenal gland is a common site of cancer metastasis, with a reported incidence of up to 36% in post-mortem studies [1]. Adrenal metastases start as microscopic foci that are not detectable by imaging until they grow and become a discrete mass. The ability to identify an adrenal metastasis at an earlier stage, before macroscopically evident at standard imaging, would allow earlier institution of appropriate therapy and thus potentially improve patient outcomes.Benitah et al [2] found no significant association between adrenal gland morphology at baseline CT and the subsequent development of adrenal metastasis at CT in patients with primary lung carcinoma. In addition to lung cancer, breast cancer and melanoma are two of the more common primary solid tumours that metastasise to the adrenal gland [3,4]. Up to 50% of melanoma patients develop adrenal metastases, the majority of which are clinically silent [5]. Survival may be prolonged in patients whose adrenal metastases are resected [4]. No data regarding the prognostic significance of baseline adrenal morphology at CT in patients with melanoma or breast carcinoma have been reported, to our knowledge.The purpose of our study was to assess whether minor changes in adrenal morphology at baseline CT represent the presence of early adrenal metastasis in patients with lung carcinoma, breast carcinoma or melanoma. Methods and materials PatientsThis United States Health Insurance Portability and Accountability Ac...