Interestingly, patients receiving vaccination and/or developing influenza infection showed a better overall survival

Interestingly, patients receiving vaccination and/or developing influenza infection showed a better overall survival. (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Conclusions Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population. values less than 0.05 were considered statistically significant. Kaplan Meier statistics was used for survival rates. Statistical analysis was performed with the GraphPad Prism Version 7.0 (GraphPad Software, Inc., La Jolla, CA) and IBM SPSS Statistis Version 22 (IBM, Armonk, NY). Results Patient characteristics For this observational study, we included 23 patients with solid cancers at two institutions in Switzerland (University Hospital Basel and Cantonal Hospital of Lucerne). Median time from initiation of PD-1 blocking antibodies to vaccination was 74?days (range, 4C457?days). Patient characteristics are depicted in Table?1. At the time of analysis, 15/23 (65.2%) patients were still alive. 2/23 (8.7%) patients were still undergoing treatment with the immune checkpoint inhibitor. 11/23 (47.8%) patients had a radiological objective response to immune checkpoint inhibition, while another 5/23 (21.7%) patients had disease stabilization (Table?2). Fourteen patients (60.9%) had a clinical benefit of treatment defined as radiographic response or stable disease for at least 6?months. Median overall survival (OS) in the whole cohort for metastatic disease was 73.5?months. In the subgroup of NSCLC patients median OS is not yet reached. After a Isobavachalcone mean follow-up of 37.5?months, Isobavachalcone 10 out of 16 NSCLC patients are still alive. No influenza infection was diagnosed in any of the vaccinated patients in our cohort during the influenza season 2015/2016. The retrospective control cohort to compare the frequency of irAEs consisted of 40 patients with metastatic NSCLC treated with PD-1 inhibitors. Table 1 Patient characteristics test, ***test Safety of vaccination The rate of local irritation (all grades) in the area of the vaccine injection in the deltoid muscle was not significantly different to healthy controls (data not shown). While no severe adverse events attributable to influenza vaccination were noted in the patient population during the first 30?days after vaccination, the overall frequency of irAEs was unusually high at 52.2% and 6 out of 23 patients (26.1%) had severe grade 3/4 Mouse monoclonal to CD81.COB81 reacts with the CD81, a target for anti-proliferative antigen (TAPA-1) with 26 kDa MW, which ia a member of the TM4SF tetraspanin family. CD81 is broadly expressed on hemapoietic cells and enothelial and epithelial cells, but absent from erythrocytes and platelets as well as neutrophils. CD81 play role as a member of CD19/CD21/Leu-13 signal transdiction complex. It also is reported that anti-TAPA-1 induce protein tyrosine phosphorylation that is prevented by increased intercellular thiol levels irAEs (Table?3). The most common side effects (all grades) were rash (outside the vaccination site) (13%), arthritis (13%), and colitis (8.7%) (Table?4). We also observed rare and unusual side effects. Two patient developed encephalitis and one patient a peripheral neuropathy. Patient 010 (male, NSCLC) was operated on a new solitary brain lesion occurring 6.3?months after initiation of nivolumab therapy and 2.0?months after influenza vaccination after having achieved stable disease. Histologically the brain lesion was necrotisizing encephalitis without evidence of tumor cells. Patient 011 (female, NSCLC) was diagnosed with an axonal impairment of the nervus medianus right 6.5?months after treatment start with nivolumab and 5.1?months after influenza vaccination. Radiologically there was no evidence of tumor infiltration, analysis of intraspinal fluid revealed a lymphocytosis without evidence of malignant cells. Anti-GD1a ganglioside antibodies were elevated 2.5-fold. Corticosteroids did not result in symptom improvement. After therapy with intravenous immunoglobulins neuropathy showed complete remission. Median time from initiation of immune checkpoint blockade to the occurrence of the irAE was 6.7?months (range, 1.8C24.6?months). All reported irAEs occurred after influenza vaccination. Median time from vaccination to occurrence of irAEs was 3.2?months (range, 0C10.6?months). In two patients the irAE occurred within the first 30?days after vaccination in all other irAEs occurred with a delay of more than one months after influenza vaccination. This frequency is significantly higher than published safety data of PD-1 checkpoint blockade trials [3, 4, 18] and also significantly higher than in a cohort of 40 metastatic NSCLC patients treated with PD-1 inhibitors at our center (all Isobavachalcone grades 25.49%, grade 3 or 4 4 at 9.8%). We also observed a trend for increasing CXCL9, CXCL10, and CCL17 levels in patients, who developed irAEs compared to patients without side effects (Fig.?3a-c). Interestingly, the only significant difference was an increase of CCL2 in patients without.