Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study

Alessio Cortellini, Sebastiano Buti, Melissa Bersanelli, Raffaele Giusti, Fabiana Perrone, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Antonino Grassadonia, Katia Cannita, Alessandra Tessitore, Federica Zoratto, Enzo Veltri, Francesco Malorgio, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Andrea BotticelliGian Carlo Antonini Cappellini, Federica De Galitiis, Maria Giuseppa Vitale, Francesca Rastelli, Federica Pergolesi, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Daniela Iacono, Maria Rita Migliorino, Alain Gelibter, Mario Alberto Occhipinti, Francesco Martella, Alessandro Inno, Stefania Gori, Sergio Bracarda, Cristina Zannori, Claudia Mosillo, Alessandro Parisi, Giampiero Porzio, Domenico Mallardo, Maria Concetta Fargnoli, Marcello Tiseo, Daniele Santini, Paolo A. Ascierto, Corrado Ficorella

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We investigate the role of family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN), during anti-PD-1/PD-L1 immunotherapy. Design: This was a multicenter retrospective study of advanced cancer patients treated with anti-PD-1/PD-L1 immunotherapy. FHC was collected in lineal and collateral lines, and patients were categorized as follows: FHC-high (in case of cancer diagnoses in both the lineal and collateral family lines), FHC-low (in case of cancer diagnoses in only one family line), and FHC-negative. Patients were also categorized according to the diagnosis of MN as follows: MN-high (>2 malignancies), MN-low (two malignancies), and MN-negative. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of immune-related adverse events (irAEs) of any grade were evaluated. Results: 822 consecutive patients were evaluated. 458 patients (55.7%) were FHC-negative, 289 (35.2%) were FHC-low, and 75 (9.1%) FHC-high, respectively. 29 (3.5%) had a diagnosis of synchronous MN and 94 (11.4%) of metachronous MN. 108 (13.2%) and 15 (1.8%) patients were MN-low and MN-high, respectively. The median follow-up was 15.6 months. No significant differences were found regarding ORR among subgroups. FHC-high patients had a significantly longer PFS (hazard ratio [HR] = 0.69 [95% CI: 0.48–0.97], p =.0379) and OS (HR = 0.61 [95% CI: 0.39–0.93], p =.0210), when compared to FHC-negative patients. FHC-high was confirmed as an independent predictor for PFS and OS at multivariate analysis. No significant differences were found according to MN categories. FHC-high patients had a significantly higher incidence of irAEs of any grade, compared to FHC-negative patients (p =.0012). Conclusions: FHC-high patients seem to benefit more than FHC-negative patients from anti-PD-1/PD-L1 checkpoint inhibitors.

Original languageEnglish
Article number1710389
JournalOncoImmunology
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • DDR genes
  • Family history of cancer
  • immune checkpoint inhibitors
  • immunotherapy
  • multiple neoplasms
  • PD-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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