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

Cortellini, A.; Buti, S.; Bersanelli, M.; Giusti, R.; Perrone, F.; Di Marino, P.; Tinari, N.; De Tursi, M.; Grassadonia, A.; Cannita, K.; Tessitore, A.; Zoratto, F.; Veltri, E.; Malorgio, F.; Russano, M.; Anesi, C.; Zeppola, T.; Filetti, M.; Marchetti, P.; Botticelli, A.; Cappellini, G. C. A.; De Galitiis, F.; Vitale, M. G.; Rastelli, F.; Pergolesi, F.; Berardi, R.; Rinaldi, S.; Tudini, M.; Silva, R. R.; Pireddu, A.; Atzori, F.; Iacono, D.; Migliorino, M. R.; Gelibter, A.; Occhipinti, M.; Martella, F.; Inno, A.; Gori, S.; Bracarda, S.; Zannori, C.; Mosillo, C.; Parisi, A.; Porzio, G.; Mallardo, D.; Fargnoli, M. C.; Tiseo, M.; Santini, D.; Ascierto, P. A.; Ficorella, C.

doi:10.1080/2162402X.2019.1710389

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.

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 / Cortellini, A.; Buti, S.; Bersanelli, M.; Giusti, R.; Perrone, F.; Di Marino, P.; Tinari, N.; De Tursi, M.; Grassadonia, A.; Cannita, K.; Tessitore, A.; Zoratto, F.; Veltri, E.; Malorgio, F.; Russano, M.; Anesi, C.; Zeppola, T.; Filetti, M.; Marchetti, P.; Botticelli, A.; Cappellini, G. C. A.; De Galitiis, F.; Vitale, M. G.; Rastelli, F.; Pergolesi, F.; Berardi, R.; Rinaldi, S.; Tudini, M.; Silva, R. R.; Pireddu, A.; Atzori, F.; Iacono, D.; Migliorino, M. R.; Gelibter, A.; Occhipinti, M.; Martella, F.; Inno, A.; Gori, S.; Bracarda, S.; Zannori, C.; Mosillo, C.; Parisi, A.; Porzio, G.; Mallardo, D.; Fargnoli, M. C.; Tiseo, M.; Santini, D.; Ascierto, P. A.; Ficorella, C.. - In: ONCOIMMUNOLOGY. - ISSN 2162-4011. - 9:1(2020), pp. 1-10. [10.1080/2162402X.2019.1710389]