Table 2.
Safety profiles of immune checkpoint inhibitors in studies in various cancers
| Tumor type | Author | Study phase |
Patient no. |
Treatment | Tumor marker | Overall AEs | Grade ≥3 AEs | Nephrotoxic AE |
Grade ≥3 nephro- toxic AEs |
|---|---|---|---|---|---|---|---|---|---|
| Solid | Topalian et al. [11] | I | 296 | Nivolumab (anti-PD-1) | PD-L1 expression | 41% | 14% | NR | NR |
| Melanoma | Weber et al. [34] | I | 90 | Nivolumab (anti-PD-1) | PD-L1 expression | NR | 5.6% | 0 | 0 |
| Solid | Brahmer et al. [12] | I | 207 | Anti-PD-L1 | NA | 39% | 9% | 0 | 0 |
| Melanoma | Hamid et al. [35] | I | 135 | Lambrolizumab (anti-PD-1) | NA | 79% | 13% | 2% | 1% (RF) |
| Melanoma | Robert et al. [32] | I | 173 | Pembrolizumab (anti-PD-1) | NA | 82% | 12% | 0 | 0 |
| Melanoma | Robert et al. [36] | I | 834 | Pembrolizumab (q2, q3w) vs ipilimumab (anti-CTLA-4) | NA | 79.5%/72.9%/ 73% |
13.3%/10.1 %/19.9% | 0/0.4%/0.4% | 0/0/0.4% |
| Hodgkin’s lymphoma | Ansell et al. [37] | I | 23 | Nivolumab | PD-L1 /2± | 78% | 22% | NR | NR |
| Melanoma | Dummer et al. [38] | II | 540 | Pembrolizumab 2 vs 10 mg/kg | NA | NR | 11 %/14% | NR | NR |
| Melanoma | Long et al. [39] | I | 418 | Nivolumab | PD-L1 ± | NR | 12% | NR | NR |
| Melanoma | Postow et al. [40] | I | 142 | Nivolumab+ ipi vs ipi | PD-L1 ± | 91 %/93% | 54%/24% | 3.1 %/2.1 % | 1 %/0% |
| Melanoma | Eggermont et al. [41] | III | 951 | Ipi vs placebo | NA | 98.7%/91 % | 55.4%/26.1 % | NR | NR |
| Solid tumor | Herbst et al. [15■] | I | 277 | Anti-PD-Ll | PD-L1 ± | 70% | 12.6% | NR | NR |
| Lung (squamous) | Rizvi et al. [42] | II | 117 | Nivolumab | PD-L1 expression | 74% | 17% | NR | NR |
| NSCLC | Gettinger et al. [43] | I | 129 | Nivolumab | NA | 41.1% | 4.7% | 3.1% | 0 |
| Renal cell carcinoma | Motzer et al. [44] | II | 168 | Nivolumab 0.3/2/10 mg/kg | PD-L1 expression | 75%/67%/78% | 5%/17%/13% | 2%/0/2% | 0 |
| Melanoma | Weber et al. [45] | III | 268 | Nivolumab | PD-L1 expression | 67.5% | 9% | NR | NR |
| Follicular lymphoma | Westin et al. [46] | II | 32 | Pidilizumab (anti-PD-Ll) | NA | NR | 0 | 0 | 0 |
| Diffuse large B-cell lymphoma | Armand et al. [47] | II | 66 | Pidilizumab | NA | 96% | 58% | 3% (RF) | 3% (RF) |
| Melanoma | Topalian et al. [48] | I | 107 | Nivolumab | NA | 84.1% | 22.4% | 2.8% (2 RF, 1 AIN) | 0 |
| Melanoma | Hodi et al. [19] | III | 540 | Ipi + gp100 vs ipi | NA | 98.4%/96.9% | 45.5%/45.8% | NR | NR |
| Head and neck cancer | Seiwert et al. [49] | Ib | 60 | Pembrolizumab | PD-L1 + | 78.3% | 55% | NR | NR |
| Bladder | Powles et al. [14■■] | I | 67 | MPDL3280A (anti-PD-L1) | PD-L-1 ± | 57% | 4% | 0 | 0 |
| Bladder | Plimack et al. [33■■] | Ib | 29 | Pembrolizumab (anti-PD-1) | PD-L-1 ± | 61% | 12% | 0 | 0 |
AE, adverse event; AIN, acute interstitial nephritis; ipi, ipilimumab; NA, not applicable; NR, not reported; NSCLC, nonsmall cell lung cancer; PD-1, programmed death-1; PD-L1, programmed death ligand-1; RF, renal failure.