Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al.: BMC Med 2016;14: 20], metastatic non-small cell lung cancer [Guibert and Mazières: Expert Opin Biol Ther 2015;15: 1789–1797], metastatic renal cell cancer [Farolfi et al.: Expert Opin Drug Metab Toxicol 2016;12: 1089–1096], and relapsed or refractory classic Hodgkin’s lymphoma [Villasboas and Ansell: Expert Rev Anticancer Ther 2016;16: 5–12]. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently [Kong et al.: Melanoma Res 2016;26: 202–204; Schwab et al.: Case Rep Oncol 2016;9: 373–378; Tardy et al.: Hematol Oncol 2016, DOI: 10.1002/hon.2338]. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.

Background: Takotsubo cardiomyopathy is a syndrome of transient left ventricular dysfunction following acute emotional or physical stress without obstructive coronary artery disease. The leading hypothesis for the etiology is stress-induced catecholamine surge. Hypothesis: People taking outpatient β-adrenergic receptor antagonist therapy have less-severe presentation and clinical course of Takotsubo cardiomyopathy. Methods: We identified patients diagnosed with Takotsubo cardiomyopathy from October 2005 to January 2011 by analyzing our cardiac-catheterization database. Clinical records and angiograms were reviewed by 2 experienced observers independently to confirm the diagnosis. We collected clinical, demographic, laboratory, and angiographic data for the identified patients. We then compared the severity of myocardial dysfunction or damage (cardiac enzymes, left ventricular end diastolic pressure, and left ventricular ejection fraction) between patients taking outpatient β-adrenergic antagonist therapy upon admission vs those who were not. Arrival and peak values for cardiac enzymes were analyzed when available. Analysis of parameters related to the severity of myocardial dysfunction or damage was conducted using the Mann-Whitney U test. Means for age were compared using the Student t test. Statistical significance was set at P< 0.05 (2-tailed). Results: Out of 64 patients identified, 16 (25%) were on one of 3 β-adrenergic antagonists on presentation: metoprolol succinate, metoprolol tartrate, or atenolol, with mean doses of 75 mg daily, 52.5 mg twice daily, and 37.5 mg daily, respectively. Patients on β-blockers were older (mean age 73.1 years vs 66 years; P < 0.05). There was no statistically significant difference in levels of cardiac enzymes, left ventricular end diastolic pressure, or left ventricular ejection fraction between the 2 groups. Conclusions: Prior therapy with low-dose β-adrenergic antagonists does not affect the severity of presentation and clinical course of Takotsubo cardiomyopathy as measured by common markers of myocardial dysfunction.

Polygenic IgG autoantibodies are implicated in majority of the cases of warm autoimmune hemolytic anemia (WAIHA). In some of these cases, complement (C3) proteins accompany the IgG antibodies. WAIHA mediated by C3 alone is relatively rare. We present an interesting case of WAIHA with a direct antiglobulin test (DAT) positive for C3 but negative for IgG in a 79-year-old woman and perform an analytical literature review of the incidence and severity of this clinical entity.

Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer.

The US FDA has recently approved an updated nivolumab dosing schedule, a single 480 mg iv. dose every 4 weeks [ 1 ], across all its previously approved indications, including second-line therapy for metastatic renal cell carcinoma. As this regimen is still in its infancy, we have not yet observed significant differences in immune-related toxicities and have not yet identified clinical characteristics which would predict intolerance and increased risk for complications. Herein, we present a patient with metastatic renal cell carcinoma who developed bullous pemphigoid after a single 480 mg iv. dose of nivolumab after previously tolerating a 240 mg biweekly dose for 2 years.