TABLE 1.
Summary of the studies assessing generic autoantibodies as predictors of immune-related adverse events in patients on immune checkpoint inhibitors.
| Study and reference | Design | Sample size | Type of immune checkpoint inhibitor | Pan-tumor | Autoantibody panel (status assessed a ) | Main results |
|---|---|---|---|---|---|---|
| Toi et al. (2019) 108 | Retrospective Single center | 137 | Nivolumab or Pembrolizumab | No (NSCLC) | ANA, RF, and ATA (preexisting) | Autoantibodies were associated with: a higher risk of irAEs (OR 3.25, p = 0.001) and a longer PFS (HR 0.53, p = 0.002) |
| Yoneshima et al. (2019) 110 | Retrospective Single center | 83 | Nivolumab or Pembrolizumab | No (NSCLC) | ANA (preexisting) | ANAs were not associated with irAEs, though the risk of irAEs tended to be higher with higher titers of ANAs. ANAs were associated with: a shorter PFS (HR 2.06, p = 0.02) and a shorter OS (HR 2.31, p = 0.03) |
| Sakakida et al. (2020) 111 | Retrospective Single center | 191 | Nivolumab, Pembrolizumab, Atezolizumab or Durvalumab | Yes | ANA (preexisting) | ANAs were not associated with irAEs, except for colitis (22 vs. 1.6%, p = 0.002). ANAs were not associated with ORR or DCR. |
| De Moel et al. (2019) 112 | Retrospective Two centers | 133 | Ipilimumab (100% of patients), Pembrolizumab or Nivolumab (49.6% of patients) | No (melanoma) | ANA, anti-dsDNA antibody, ENA b , RF, ACPA, ASMA, AMA, anti-LKM antibody, and ATA (development) | Autoantibodies were associated with: a trend for higher risk of irAEs (OR 2.92, p = 0.12) and for better OS (HR 0.66, p = 0.21) ATAs were associated with: higher ORR (OR 5.43, p = 0.021) |
| Giannicola et al. (2019) 113 | Retrospective Multicenter | 92 | Nivolumab | No (NSCLC) | ANA, ENA c ,and ASMA (short-term development, within 30 days) | Early detection of autoantibodies was associated with: a higher risk of irAEs (HR not available, p = 0.002), a higher PFS (HR 0.23, p = 0.004) and a higher OS (HR 0.28, p = 0.030) |
| Les et al. (2021) 114 | Retrospective Single center Pilot-study | 69 | Nivolumab | Yes | ANA, RF, and ANCA (preexisting and development) | Autoantibodies were associated with a higher risk of irAE (OR 46.61, p = 0.010) |
| AUTENTIC | Prospective Multicenter | 294 | All approved immune checkpoint inhibitors | Yes | ANA, RF, and ANCA (preexisting and development) | - |
a
Status assessed: preexisting antibodies (at baseline), and/or the development of antibodies (during treatment).
b
Using U1RNP, SS-A/Ro, SS-B/La, centromere B, Scl-70, Jo-1, and Sm proteins as antigens.
c
The antigens used in this panel were not specificed by the study authors.