Glycemic disorders in melanoma patients treated with anti-PD1.

Abstract

9525 Background: Anti-PD1 are now the backbone of immunotherapy (IT) of metastatic melanoma (MM). Although they are overall well- tolerated, a number of severe immune-related adverse events (IRAE) have been described, among which type 1 diabetes. We observed 3 cases of fulminant diabetes (FD) in our center, and also had the impression that diabetics patients became more difficult to manage when receiving anti-PD1. Methods: Retrospective analysis of blood glucose samples collected before, during and after anti-PD1 treatment (trt ) in all mm patients (pts) receiving anti-PD1 in our department over a 36-month period. Study of FD cases observed. Results: A total of 163 pts were treated with 1920 cures of anti-PD1 including 27 treated within clinical trials. Anti-PD1 was the 1st line of IT in 70% of cases. As a whole, 1470 glycaemia were available. There was no significant difference between the median pre and post-trt glycaemia (5.37 +/-1.6 vs 5.6 +/-1.3 mmol/L (p = 0.033)). In the 28 pts with a type I (n = 0) or II (n = 28) diabetes prior to trt, there was very slight drift toward an increase of glycaemia along with the successive trt infusions (+0.05mmol/L/Cure, p = 0.004 with linear regression tendency test) .Three pts (1.84%) developed a FD revealed by a severe episode of ketosis with acute polyuria polydipsia, hyperglycaemia until 50mmol/L and weight loss. Two additional cases of FD were observed in pts treated within clinical trial comparing anti-PD1 with anti-CTLA4 in adjuvant and metastatic situation (imputability of anti-PD1 likely but uncertain until unblinding). None of these pts had any glucose increase in weeks prior to FD diagnosis. Four out of 5 FD cases had an HLA group at risk for type 1 diabetes development (HLA DRB3/4), a rare group in general population (1%). Conclusions: We could not document any systematic tendency to glycemic disorder in mm pts treated by anti-PD1. In diabetic pts prior to trt, a slight drift toward increase of glycaemia may be explained by other interfering factors (diet, metastatic disease itself, corticosteroids, anxiety etc). FD is not exceptional (2% of patients in our series) and does not seem to be announced by any minor preliminary glycemic disorder. Despite apparently stochastic onset, FD may be associated with HLA DRB3/4 subgroup.