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
| العنوان: | 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 |
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| المؤلفون: | Eleonora Iuliano, Andrea Sergi, Pierpaolo Correale, Giovanna Bianco, Amalia Luce, Alessia Stranges, Maria Antonietta Mazzei, Rita Emilena Saladino, Pierpaolo Pastina, Pierfrancesco Tassone, M. Altomonte, Rocco Giannicola, Paolo Tini, Natale Daniele Calandruccio, Pierosandro Tagliaferri, Michele Caraglia, Daniele Caracciolo, Luigi Pirtoli, Valerio Nardone, Diana Giannarelli |
| المصدر: | Journal of Clinical Oncology. 38:e15094-e15094 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, business.industry, Cancer, medicine.disease, Immune checkpoint, HLA-B, Blockade, Oncology, Immunology, Medicine, Aseptic processing, Allele, business, Pneumonitis |
| الوصف: | 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. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::158950d7652285895704d36e3f1f82c9Test https://doi.org/10.1200/jco.2020.38.15_suppl.e15094Test |
| رقم الانضمام: | edsair.doi...........158950d7652285895704d36e3f1f82c9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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