Hemophagocytic lymphohistiocytosis in advanced melanoma treated with dabrafenib and trametinib combination: two cases.

Hemophagocytic lymphohistiocytosis (HLH) has been only rarely reported in patients with BRAF-mutated advanced melanoma treated with targeted therapies and never with first-line dabrafenib/trametinib combination thus far. Two patients treated with first-line dabrafenib and trametinib combination therapy for metastatic melanoma presented with sudden occurrence of fever, cytopenia, rhabdomyolysis, hepatic cytolysis, hypertriglyceridemia and very high ferritin levels after few weeks of treatment, associated with concomitant epstein-barr virus (EBV) reactivation in one patient. In both cases, drug-induced HLH was primarily considered owing to a high H-score and the absence of other etiology. Patients rapidly improved after treatment discontinuation associated with oral steroids in one patient and did not relapse after subsequent treatment resumption with a concurrent anti-BRAF/anti-MEK combination. In metastatic melanoma HLH may occur either spontaneously in the absence of any treatment as a paraneoplastic condition, related to an intercurrent infection or drug-induced mainly with various immunotherapy or with dabrafenib and trametinib following immunotherapy. However, such observations are scarce and these are the first cases of HLH occurring during first-line treatment with dabrafenib and trametinib in advanced melanoma to our knowledge. Pathomechanisms remain to be elucidated since triggering factors may encompass the treatment itself but also other significant actors including viral reactivation along with the underlying disease. The liability of treatment should be considered in cases of HLH occurring in patients with advanced melanoma successfully treated with a combined targeted therapy. A rechallenge with a concurrent anti-BRAF/anti-MEK can be proposed in this setting.

Collaboration between cardiologist and clinical pharmacist on prescription quality: What is the potential clinical impact for cardiology patients?

OBJECTIVES: The aim of this study was to determine the effect of pharmacists' interventions (PI) on the potential clinical impact of medication errors, including the lack of therapeutic optimisation of patients with cardiologic diseases, such as heart failure and acute coronary syndrome). METHODS: This was an observational, prospective study conducted in the cardiology department of a French university hospital centre for a duration of 9 months. All prescriptions were analysed and PI were registered for clinical rating by pharmacists and cardiologist. RESULTS: A total of 532 PI cases were recorded in 339 patients, with a mean of 1.57 (±1.04) PI. The PI acceptance rate was 98.1%. "Dose adjustment" and "introduction therapy" were the most common interventions and represented 38.0% and 32.9%, respectively, of all PI. Statins were the most frequently involved drugs (18.1%), followed by ACE (Angiotensin Converting Enzyme) inhibitors (10.9%) and antiplatelet agents (9.3%). Moreover, 13.8% of PI potentially avoided a severe or very severe clinical impact (n = 71) and 38.6% had a significant impact altering the quality of life (n = 198). There was no significant difference between the average score performed by the clinical pharmacist included in the cardiology team and the one obtained by the cardiologist (P = .797). In contrast, a significant difference was observed for the average score established by the pharmacist localised in central pharmacy versus the rating of the cardiologist (P < .001). CONCLUSIONS: The collaboration between clinical pharmacists and cardiologists in the medical units seems to be beneficial to the quality of prescriptions, including the implementation of recommendations. The good rate of PI acceptance and the similar rating with the cardiologist show that there is a change in perspective of the pharmacist, being closer to the clinical reality.