OncoImmunology (Jan 2020)

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 Botticelli,
  • Gian 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

DOI
https://doi.org/10.1080/2162402X.2019.1710389
Journal volume & issue
Vol. 9, no. 1

Abstract

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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.

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