Correlation Of Hla-B*35 And Drb1*11 Alleles With A High Risk Of Interstitial Aseptic Pneumonitis In Cancer Patients Receiving Pd-1/Pdl1 Immune-Checkpoint Blockade.

e15094 Background: Tumor infiltrating CTL-rescue by PD-1/PDL1 immune-checkpoint blockade is a recommended treatment for several malignancies including non-small-cell-lung-cancer (NSCLC), malignant melanoma, head and neck, kidney, and urothelial cancer. MAbs to either PD-1 (Nivolumab and Pembrolizumab) or PDL1 (Atezolizumab and Durvalumab) are considered as active drugs in these patients, however, their use may be complicated by unpredictable immune-related adverse events (irAEs) and in less extent by a dreaded interstitial aseptic pneumonitis (IAP). Methods: We carried out a retrospective multi-institutional analysis aimed to investigate possible clinical and biological parameters correlated with the occurrence of IAP in a cohort of 256 cancer patients (188 with mNSCLC and 78 with other malignancies) who received PD-1/PDL-1 blockade since November 2015. Association of IAP with clinical/biological factors was assessed by the chi-square test. Statistics were performed by the SPSS software 23.0. HLA molecular analysis was performed by reverse SSO DNA typing assays on patients’ PBMCs. Results: A centralised radiological review recorded a IAP in 29 patients (11.3%) whose 15 (5.8%) were free of symptoms. There was no correlation of IAP risk with tumor type, specific PD-1 or PDL1 blocking mAb, radiation therapy, inflammatory markers, and other irAEs. IAP was more frequent in males than females [RR = 2.03, (95% CI: 0.63-5.61) p > 0.05] and occurred more often in mNSCLC patients who had received metronomic chemotherapy +/- bevacizumab [RR = 3.05 (95% CI: 1.32-7.06),P = 0.005] or TKI [RR = 1.73 (95% CI: 0.75-4.00),P > 0.05] compared with other treatments prior PD-1/PDL1 blockade. Finally, IAP occurrence was strictly correlated to the expression of HLA-B*35 [RR = 1.73 (95% CI: 0.81-3.71) P < 0.05] and DRB1*11 [RR = 2.34 (95% CI: 1.02-5.39); P = 0.03], two alleles associated to common autoimmune diseases. Conclusions: Taken together, our findings may have relevant implications in predicting the risk of IAP in mNSCLC receiving PD-1/PDL1 blockade and provide the rationale for further immunological and clinical investigations.