A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable
Open accessAbstract
BACKGROUND: Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. PATIENTS AND METHODS: We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (< 25). A gender analysis was also performed, using the same binomial cut-off. Further subgroup analyses were performed categorizing patients into underweight, normal weight, overweight and obese. RESULTS: Between September 2013 and May 2018, 976 patients were evaluated. The median age was 68 years, male/female ratio was 663/313. Primary tumors were: NSCLC (65.1%), melanoma (18.7%), renal cell carcinoma (13.8%) and others (2.4%). ECOG-PS was ≥2 in 145 patients (14.9%). PD-1/PD-L1 inhibitors were administered as first-line treatment in 26.6% of cases. Median BMI was 24.9: 492 patients (50.6%) were non-overweight, 480 patients (50.4%) were overweight/obese. 25.2% of non-overweight patients experienced irAEs of any grade, while 55.6% of overweight/obese patients (p < 0.0001). ORR was significantly higher in overweight/obese patients compared to non-overweight (p < 0.0001). Median follow-up was 17.2 months. Median TTF, PFS and OS were significantly longer for overweight/obese patients in univariate (p < 0.0001, for all the survival intervals) and multivariate models (p = 0.0009, p < 0.0001 and p < 0.0001 respectively). The significance was confirmed in both sex, except for PFS in male patients (p = 0.0668). CONCLUSIONS: Overweight could be considered a tumorigenic immune-dysfunction that could be effectively reversed by ICIs. BMI could be a useful predictive tool in clinical practice and a stratification factor in prospective clinical trials with ICIs.
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Obesity is associated with improved responses to immune checkpoint blockade and survival in melanoma, NSCLC, and other solid tumors, despite its association with poor overall outcomes.
“While obesity is associated with oncogenesis and poor outcomes overall, it has interestingly been associated with improved responses to ICB and survival in patients with melanoma, NSCLC, and other solid tumors”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Cortellini et al., 2019
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- Authors
- Cortellini, A., Bersanelli, M., Buti, S., Cannita, K., Santini, D., Perrone, F., Giusti, R., Tiseo, M., Michiara, M., Di Marino, P., Tinari, N., De Tursi, M., Zoratto, F., Veltri, E., Marconcini, R., Malorgio, F., Russano, M., Anesi, C., Zeppola, T., Filetti, M., Marchetti, P., Botticelli, A., Antonini Cappellini, G. C., De Galitiis, F., Vitale, M. G., Rastelli, F., Pergolesi, F., Berardi, R., Rinaldi, S., Tudini, M., Silva, R. R., Pireddu, A., Atzori, F., Chiari, R., Ricciuti, B., De Giglio, A., Iacono, D., Gelibter, A., Occhipinti, M. A., Parisi, A., Porzio, G., Fargnoli, M. C., Ascierto, P. A., Ficorella, C., & Natoli, C.
- Affiliations
- University of L'Aquila (IT)
- University of Parma (IT)
- Università Campus Bio-Medico (IT)
- Marche Polytechnic University (IT)
- Corresponding author
- Cortellini, Alessio
- ORCID
- Cortellini, Alessio
- Bersanelli, Melissa
- Buti, Sebastiano
- Cannita, Katia
- Santini, Daniele
- Perrone, Fabiana
- Giusti, Raffaele
- Tiseo, Marcello
- Tinari, Nicola
- Zoratto, Federica
- Veltri, Enzo
- Marconcini, Riccardo
- Russano, Marco
- Zeppola, Tea
- Filetti, Marco
- Marchetti, Paolo
- Botticelli, Andrea
- Vitale, Maria Giuseppa
- Pergolesi, Federica
- Berardi, Rossana
- Rinaldi, Silvia
- Atzori, Francesco
- Chiari, Rita
- Ricciuti, Biagio
- Iacono, Daniela
- Gelibter, Alain
- Occhipinti, Mario Alberto
- Parisi, Alessandro
- Porzio, Giampiero
- Ascierto, Paolo Antonio
- Ficorella, Corrado
- Natoli, Clara
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2019-02-27
- Volume
- 7
- Issue
- 1
- Pages
- 57-57
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC6391761
- OpenAlex
- W2925088208
- Cited by
- 413
- References
- 45
- Citations by year
- 2026: 32 · 2025: 40 · 2024: 52 · 2023: 63 · 2022: 71 · 2021: 75 · 2020: 60 · 2019: 20
- FWCI
- 23.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion, public-domain)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Health Sciences › Health Professions › Pharmacy › Obesity and Health Practices
- Keywords
- body mass index, overweight, obesity, immune checkpoint inhibitors, immune-related adverse events, objective response rate, survival outcomes, advanced cancer, non-small cell lung cancer, melanoma, renal cell carcinoma, predictive biomarkers, sex differences, immune dysfunction, first-line therapy, prognostic factors
- MeSH terms
- Antineoplastic Agents, Immunological, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Neoplasm Staging, Neoplasms, Obesity, Biomarkers, Tumor, Body Mass Index, Proportional Hazards Models, Treatment Outcome, Overweight, Kaplan-Meier Estimate, Young Adult, Molecular Targeted Therapy, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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