Table 3. Factors associated with recurrence of pneumonitis in patients after ICI rechallenge.
| Variable | CIP recurrence (n=9) | CIP non-recurrence (n=36) | P value |
|---|---|---|---|
| Age (years), median [range] | 65 [55–75] | 66 [36–85] | 0.79 |
| Male, n (%) | 9 (100.0) | 28 (77.8) | 0.18 |
| Initial ICI type, n (%) | 0.57 | ||
| Anti-PD-1 | 9 (100.0) | 32 (88.9) | |
| Anti-PD-L1 | 0 | 4 (11.1) | |
| Initial treatment data, n (%) | 0.011 | ||
| Monotherapy | 2 (22.2) | 3 (8.3) | |
| Combination with chemotherapy | 2 (22.2) | 27 (75.0) | |
| Combination with anti-angiogenesis | 2 (22.2) | 1 (2.8) | |
| Combination with chemotherapy and anti-angiogenesis | 3 (33.3) | 5 (13.9) | |
| Median time to first CIP (months) (range) | 3.8 (1.5–5.3) | 2.6 (0.7–13.9) | 0.55 |
| ECOG PS (≥2) at first CIP, n (%) | 7 (77.8) | 13 (36.1) | 0.057 |
| Severe grade of first CIP, n (%) | 4 (44.4) | 1 (2.8) | 0.004* |
| Radiological features, n (%) | 0.24 | ||
| COP | 4 (44.4) | 9 (25.0) | |
| GGO | 1 (11.1) | 13 (36.1) | |
| NSIP | 4 (44.4) | 7 (19.4) | |
| NOS | 0 | 4 (11.1) | |
| Unknown | 0 | 3 (8.3) | |
| Clinical type, n (%) | 0.30 | ||
| Pure | 4 (44.4) | 25 (69.4) | |
| Induced | 1 (11.1) | 3 (8.3) | |
| Mixed | 4 (44.4) | 8 (22.2) | |
| Laboratory values at rechallenge, median (range) | |||
| IL-6, pg/mL | 25 (8.1–51.6) | 7.6 (1.3–49.1) | 0.007* |
| IL-10, pg/mL | 3.5 (1.4–22.0) | 2.2 (0.8–29.9) | 0.32 |
| LDH, U/L | 262.0 (165.6–2,111.3) | 227.1 (126.8–397.0) | 0.24 |
| ALB, g/L | 35.5 (25.9–39.0) | 37.0 (28.7–43.4) | 0.54 |
| CRP, mg/L | 32.3 (10.0–107.5) | 10.1 (1.2–188.2) | 0.032* |
| KL-6, U/mL | 1,730.5 (395.0–2,385.0) | 822.5 (386.0–2,283.0) | 0.29 |
| WBC, K/μL | 10.3 (4.9–16.4) | 6.9 (4.3–15.3) | 0.022* |
| ALC, K/μL | 1.8 (0.4–3.2) | 1.3 (0.6–3.2) | 0.69 |
| AEC, K/μL | 0.1 (0–0.5) | 0.1 (0–0.4) | 0.63 |
| ANC, K/μL | 7.2 (3.2–11.7) | 4.6 (1.7–12.4) | 0.030* |
| NLR | 3.6 (2.0–24.3) | 3.5 (0.7–8.5) | 0.46 |
| Rechallenge with same ICI or ICI combination, n (%) | 7 (77.8) | 33 (91.7) | 0.26 |
| Median duration from first CIP to rechallenge (months) (range) | 1.4 (0–4.4) | 0.8 (0–5.9) | 0.43 |
| Occurrence of new irAEs, n (%) | 5 (55.6) | 6 (16.7) | 0.028* |
| Hepatitis | 3 (33.3) | 5 (13.9) | 0.33 |
| Myocarditis | 3 (33.3) | 0 | 0.036* |
| Colitis | 0 | 1 (2.8) | 1 |
| Encephalitis | 0 | 1 (2.8) | 1 |
*, P<0.05. ICI, immune checkpoint inhibitor; PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1; CIP, checkpoint inhibitor-related pneumonitis; ECOG PS, Eastern Cooperative Oncology Group performance status; COP, cryptogenic organizing pneumonitis; GGO, ground glass opacities; NSIP, non-specific interstitial pneumonia; NOS, pneumonitis not otherwise specified; IL, interleukin; LDH, lactate dehydrogenase; ALB, albumin; CRP, C-reactive protein; KL-6, Krebs von den Lungen-6; WBC, absolute white blood cell count; ALC, absolute lymphocyte count; AEC, absolute eosinophil count; ANC, absolute neutrophil count; NLR, neutrophil-to-lymphocyte ratio; irAEs, immune-related adverse events.