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Acute graft-versus-host disease (aGVHD) is a significant source of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). aGVHD targets the skin, gastrointestinal (GI) tract, and liver resulting in three key clinical features: skin rash, serum bilirubin elevation, and diarrhea. The primary objective was to identify the incidence of GI tract and liver involvement in patients with cutaneous aGVHD, and to compare mortality between skin-limited and extra-cutaneous disease.

Brentuximab vedotin (BV) is a novel antibody drug conjugate consisting of an anti- CD30 IgG1 antibody, cAC10, linked to monomethylauristatin E, a potent inhibitor of microtubule polymerization. It is approved for treatment of relapsed classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) in the US (FDA; 8/2011) and Europe (EMA; 10/2012). Peripheral neuropathy was the most frequent treatment-related adverse event (AE) in phase II trials, and the most common Grade 3 or higher toxicity apart from cytopenias. Although abdominal pain has been observed in up to 25% of all patients, pancreatitis is a previously unrecognized AE. We now report 8 cases of BV-associated pancreatitis, 2 of them fatal.

Background: We previously reported that thal and len administration was associated with high VTE rates, particularly for multiple myeloma (JAMA 2006). The Connecticut Attorney General filed a Citizen's Petition in 2005 with the FDA highlighting this safety concern. In 2006, when the FDA granted approval to thal and len to treat multiple myeloma patients, the FDA upheld much of the Petition and the sponsor included a Black Box warning to package inserts for both drugs when administered to MM patients, and encouraged consideration of VTE prophylaxis (although optimal strategies were not known). Herein, to compare the len/thal/dex-associated VTE rates pre- and post-FDA approval, the Research on Adverse Drug Events and Reports (RADAR) project performed a literary search through Pubmed and Ovid, with the search terms: “VTE,” “thrombosis,” “thromboembolism,” “DVT,” “multiple myeloma,” “thalidomide,” and “lenalidomide.”

Background: In October 2003, six months after approval of the first drug-eluting coronary stent (CYPHER™ stent), the FDA reported 50 stent-associated hypersensitivity reactions. In November 2003, FDA officials reported that these reactions were probably due to concomitantly prescribed medications. Methods: All adverse device event reports for CYPHER stent associated hypersensitivity- reactions in the FDA’s adverse event reporting system, the published literature, or from RADAR, between April 2003 and June 2004 were reviewed. Causality was evaluated using World Health Organization criteria. Results: Review of FDA reports (n=2,607) identified 161 persons with hypersensitivity symptoms. Fewer than 20 hypersensitivity cases were reported monthly, except for 43 and 42 reports in October and November 2003. Symptoms began within 2 days of stent implantation (21%), between 2 and 7 days (43%) and between 7 and 14 days (19%) following stent implantation and persisted for less than 8 days for 17%, 8–30 days for 29% and > 30 days for 55%. Findings included rash (80%), itching (28%), hives (19%), dyspnea (12%), fever (12%), chest pain (8%), anaphylaxis (7%), joint pain or swelling (7%) and high or low blood pressure (5%). Among persons with rashes, 25% covered the entire body, 21% developed hives, 7% had localized maculopapular eruptions and 4% developed blisters or desquamation. Treatment included emergency interventions (26%) or hospitalization (19%). Outcomes included permanent disability (5%) or death (2%). Aspirin or clopidogrel was discontinued at the time of hypersensitivity onset for 42. Using WHO criteria, clopidogrel, aspirin, ticlopidine and/or the stent itself were classified as possible causes for > 85% of cases. Of 150 events possibly caused by the CYPHER stent, 35 persisted for > 30 days. For 7 probable CYPHER-stent induced hypersensitivity cases identified by RADAR (n=4), the FDA (n=2) or the literature (n=1), symptom onset was < 5 days (n=3) and at 3 weeks, 1 month, 4 months, and 7 months after stent implantation. Findings included rash (n=4), hives (n=1), blisters on both hands (n=1), dyspnea (n=2), eosinophilia (n=1), elevated IgE levels (n=2) and Gallium-67 scan findings at the stent (n=1). Findings did not abate with thienopyridine discontinuation (n=5). Outcomes included resolution of symptoms with hospitalization (n=1) or corticosteroids (n=2), persistent angina (n=1) and subsequent occurrence of fatal cardiac events, with autopsy identification of eosinophilic infiltrates at the stent site (n= 2 patients). Conclusion: Rash, hives, dyspnea and catastrophic cardiac events may represent local and systemic hypersensitivity reactions from the CYPHER-stent. Reporting of these events decreased by > 90% following a FDA advisory that suggested that skin reactions were unrelated to the stent. However, our findings highlight the importance of continued vigilance for hypersensitivity reactions that may represent an early manifestation of a catastrophic hypersensitivity event.