Alessio Cortellini1, Melissa Bersanelli2, Daniele Santini3, Sebastiano Buti4, Marcello Tiseo2, Katia Cannita5, Fabiana Perrone4, Raffaele Giusti6, Michele De Tursi7, Federica Zoratto8, Riccardo Marconcini9, Marco Russano3, Tea Zeppola3, Cecilia Anesi3, Marco Filetti6, Paolo Marchetti10, Andrea Botticelli11, Alain Gelibter12, Federica De Galitiis13, Maria Giuseppa Vitale14, Francesca Rastelli15, Marianna Tudini16, Rosa Rita Silva16, Francesco Atzori17, Rita Chiari18, Biagio Ricciuti19, Andrea De Giglio19, Maria Rita Migliorino20, Domenico Mallardo21, Vito Vanella21, Claudia Mosillo22, Sergio Bracarda22, Silvia Rinaldi23, Rossana Berardi23, Clara Natoli7, Corrado Ficorella24, Giampiero Porzio24, Paolo A Ascierto21. 1. Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. Electronic address: alessiocortellini@gmail.com. 2. Medical Oncology, University Hospital of Parma, Parma, Italy; Department of Medicine and Surgery, University of Parma, Parma, Italy. 3. Medical Oncology, Campus Bio-Medico University, Rome, Italy. 4. Medical Oncology, University Hospital of Parma, Parma, Italy. 5. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. 6. Medical Oncology, St. Andrea Hospital, Rome, Italy. 7. Department of Medical, Oral & Biotechnological Sciences University G. D'Annunzio, Chieti-Pescara, Italy. 8. Medical Oncology, Santa Maria Goretti Hospital, Latina, Italy. 9. Department of Oncology, University Hospital of Pisa, Istituto Toscano Tumori, Pisa, Italy. 10. Medical Oncology, St. Andrea Hospital, Rome, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 11. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 12. Medical Oncology (B), Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy. 13. Istituto Dermopatico Dell'Immacolata, IDI-IRCCS, Roma, Italy. 14. Medical Oncology, University Hospital of Modena, Modena, Italy. 15. Medical Oncology, Fermo Area Vasta 4, Fermo, Italy. 16. Medical Oncology, AV2 Fabriano ASUR, Marche, Italy. 17. Medical Oncology Unit, University Hospital of Cagliari, Cagliari, Italy. 18. Medical Oncology, Ospedali Riuniti Padova Sud "Madre Teresa di Calcutta", Monselice, Italy. 19. Department of Surgical and Biomedical Sciences, University of Perugia, Perugia, Italy. 20. Pulmonary Oncology Unit, St. Camillo Forlanini Hospital, Rome, Italy. 21. Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori-IRCCS Fondazione "G. Pascale", Naples, Italy. 22. S.C. Medical Oncology, Azienda Ospedaliera S. Maria, Terni, Italy. 23. Oncology Clinic, Università Politecnica Delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy. 24. Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Abstract
BACKGROUND: Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancer patients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obese patients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. PATIENTS AND METHODS: We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancer patients treated with PD-1/PD-L1 inhibitors according to baseline BMI. RESULTS: One thousand and seventy advanced cancer patients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obese patients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p < 0.0001). Overweight and obese patients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obese patients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. CONCLUSIONS: Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.
BACKGROUND: Several studies have found an association between higher body mass index (BMI) and improved clinical outcomes in cancerpatients receiving programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors. In a previous study, we found that overweight/obesepatients were significantly more likely to experience any grade immune-related adverse events (irAEs) compared to non-overweight patients. PATIENTS AND METHODS: We conducted a 'real-life', multi centre, retrospective observational study aimed at comparing the incidence of irAEs among cancerpatients treated with PD-1/PD-L1 inhibitors according to baseline BMI. RESULTS: One thousand and seventy advanced cancerpatients were evaluated. The median age was 68 years (range: 21-92), male/female ratio was 724/346. Primary tumours were: non-small-cell lung carcinoma (NSCLC) (653 patients), melanoma (233 patients), renal cell carcinoma (RCC) (152 patients) and others (29 patients). Median BMI was 25 (13.6-46.6); according to World Health Organisation (WHO) classification, 44 patients (4.1%) were defined as underweight, 480 patients (44.9%) as having a normal weight, 416 patients (38.9%) as overweight and 130 patients (12.1%) as obese. Higher BMI was significantly related to higher occurrence of any grade immune-related adverse events [irAEs] (p < 0.0001), G3/G4 irAEs (p < 0.0001) and irAEs leading to discontinuation (LTD) (p < 0.0001). Overweight and obesity were confirmed predictors for irAEs of any grade at both univariate and multivariate analysis. The adjusted odds ratios (ORs) (compared to normal-weight) were 10.6; 95% confidence interval (95%CI): 7.5-14.9 for overweight, and 16.6 (95%CI: 10.3-26.7) for obesepatients. Obesity was the only factor significantly related to a higher incidence of G3/G4 irAEs (OR = 11.9 [95%CI: 6.4-22.3], p < 0.0001) and LTD irAEs (OR = 8.8 [95%CI: 4.3-18.2], p < 0.0001). Overweight and obesepatients experienced a significantly higher occurrence of cutaneous, endocrine, gastro-intestinal (GI), hepatic and 'others' irAEs, compared to normal-weight patients. Only obesepatients experienced a significantly higher occurrence of pulmonary and rheumatic irAEs, compared to normal-weight patients. CONCLUSIONS: Considering the previously evidenced association between higher BMI and better outcome, the current finding about the relationship between BMI and irAEs occurrence can contribute to consideration of these findings as the upside of the downside, which underlies an 'immunogenic phenotype'.
Authors: Marco Russano; Alessio Cortellini; Raffaele Giusti; Alessandro Russo; Federica Zoratto; Francesca Rastelli; Alain Gelibter; Rita Chiari; Olga Nigro; Michele De Tursi; Sergio Bracarda; Stefania Gori; Francesco Grossi; Melissa Bersanelli; Lorenzo Calvetti; Vincenzo Di Noia; Mario Scartozzi; Massimo Di Maio; Paolo Bossi; Alfredo Falcone; Fabrizio Citarella; Francesco Pantano; Corrado Ficorella; Marco Filetti; Vincenzo Adamo; Enzo Veltri; Federica Pergolesi; Mario Alberto Occhipinti; Linda Nicolardi; Alessandro Tuzi; Pietro Di Marino; Serena Macrini; Alessandro Inno; Michele Ghidini; Sebastiano Buti; Giuseppe Aprile; Eleonora Lai; Marco Audisio; Salvatore Intagliata; Riccardo Marconcini; Davide Brocco; Giampiero Porzio; Marta Piras; Erika Rijavec; Francesca Simionato; Clara Natoli; Marcello Tiseo; Bruno Vincenzi; Giuseppe Tonini; Daniele Santini Journal: Cancer Immunol Immunother Date: 2021-08-31 Impact factor: 6.968
Authors: Amanda Leiter; Emily Carroll; Sonia De Alwis; Danielle Brooks; Jennifer Ben Shimol; Elliot Eisenberg; Juan P Wisnivesky; Matthew D Galsky; Emily Jane Gallagher Journal: Eur J Endocrinol Date: 2021-05-10 Impact factor: 6.558
Authors: Alessio Cortellini; Biagio Ricciuti; Marcello Tiseo; Emilio Bria; Giuseppe L Banna; Joachim Gjv Aerts; Fausto Barbieri; Raffaele Giusti; Diego L Cortinovis; Maria R Migliorino; Annamaria Catino; Francesco Passiglia; Mariangela Torniai; Alessandro Morabito; Carlo Genova; Francesca Mazzoni; Vincenzo Di Noia; Diego Signorelli; Alain Gelibter; Mario Alberto Occhipinti; Francesca Rastelli; Rita Chiari; Danilo Rocco; Alessandro Inno; Michele De Tursi; Pietro Di Marino; Giovanni Mansueto; Federica Zoratto; Francesco Grossi; Marco Filetti; Pamela Pizzutilo; Marco Russano; Fabrizio Citarella; Luca Cantini; Giada Targato; Olga Nigro; Miriam G Ferrara; Sebastiano Buti; Simona Scodes; Lorenza Landi; Giorgia Guaitoli; Luigi Della Gravara; Fabrizio Tabbò; Serena Ricciardi; Alessandro De Toma; Alex Friedlaender; Fausto Petrelli; Alfredo Addeo; Giampiero Porzio; Corrado Ficorella Journal: J Immunother Cancer Date: 2020-10 Impact factor: 13.751