Table 2.
Recurrence of irAEs after ICI resumption.
| Study | NOS Scale (*) | Malignancy | Number of Retreated Patients after 1st irAE | Rechallenge Type |
% of Any 2nd irAE (New + Same irAE) |
% of Same 2nd irAE | % of Permanent ICI Discontinuation |
|---|---|---|---|---|---|---|---|
| Abou Alaiwi et al. [31] | 8 | Metastatic RCC | 36 (G ≥3: 47%) |
Resumption: Anti-PD(L)1: 67% Combination (33%) |
50% (G ≥3: 38.9%) |
16.7% | 27.8% |
| Abu Sbeih et al. [32] † | 6 | Melanoma (54%) NSCLC (16%) Genitourinary (10%) Other solids (16%) Hematologic (4%) |
167 (G ≥3 colitis: 33%) †† |
Resumption: Anti-CTLA-4 (14%) Anti-PD(L)-1 (42.5%) Switch: Anti-CTLA-4 to anti-PD(L)-1 (38.5%) Anti-PD(L)-1 to anti-CTLA-4 (5%) |
NR | 34.1% (G ≥2 colitis: 46.6%) |
NR |
| Allouchery et al. [33] | 7 | Melanoma (44%) Lung (41%) RCC (6%) Lymphoma (3%) Others (6%) |
180 (G ≥3: 49%) |
Resumption: Same ICI or ICI combination (85%) Switch (15%) |
38.9% (G ≥3: 35%) |
27.2% | 26.1% |
| Bhatlapenumarthi et al. [30] | 6 | NSCLC (44%) SCLC (11%) Melanoma (18.5%) RCC (18.5%) Anaplastic thyroid (4%) Thymic (4%) |
27 (G ≥3: 26%) |
Resumption: Anti-PD-1 (93%) Anti-PDL-1 (7%) |
33.3% (G ≥3: 55.6%) |
7.4% | NR |
| Brunot et al. [34] | 7 | Metastatic melanoma | 56 (G ≥3: 100%) |
Switch: Anti-CTLA-4 to anti-PD-1 |
35.7% (G ≥3: 60%) |
14.3% | 8.9%) |
| Cortazar et al. [35] ††† | 8 | Melanoma (36%) ¶ Lung (26%) ¶ Genitourinary (17%) ¶ Other (21%) ¶ |
31 | Resumption with the same ICI (87%) | NR | 22.6% | NR |
| de Malet et al. [36] | 7 | Melanoma (75%) ¶ NSCLC (11%) † RCC (4%) ¶ Prostate (3%) ¶ Lymphoma (3%) ¶ Cervical (3%) ¶ Colorectal (1%) ¶ Ovarian (1%) ¶ |
26 (G ≥3: 61.5%) |
Resumption: Anti-CTLA-4 (23%) Anti-PD-1 (31%) Switch: Anti-CTLA-4 to anti-PD-1 (42%) Anti-PD-1 to anti-CTLA-4 (4%) |
46.2% (G ≥3: 16.7%) |
23.1% (G ≥3: 33.3%) |
NR |
| Dolladile et al. [21] | 6 | No detail about only rechallenged patients | 452 (Serious: 92%) |
PD(L)-1 (82%) CTLA-4 (5%) Combination (13%) |
33.2% | 28.8% | 4.6% treatment-related death |
| Gobbini et al. [37] | 8 | NSCLC | 58 (G ≥3: 47%) |
Resumption: Anti-PD(L)-1 (100%) |
14.8% * | 7.4% * | NR |
| Gupta et al. [38] ††† | 8 | Melanoma (32%) Genitourinary (23%) Lung (22%) Other (22%) |
121 (Stage ≥2: 78%) |
Resumption: (81%) Switch: (19%) |
NR | 16.5% (Stage ≥2: 80%) |
0% |
| Li et al. [39] | 7 | Melanoma | 31 (G ≥3: 100%) |
Resumption: Anti-PD-1 (84%) Anti-CTLA-4 (6.5%) Anti-PDL-1 (3%) Switch: Anti-CTLA-4 to anti-PD-1 (6.5%) |
48.4% (G ≥3: 20%) |
12.9% (G ≥3: 50%) |
19.3% |
| Menzies et al. [46] | 7 | Melanoma | 67 (G ≥3: 87%) |
Switch: Anti-CTLA-4 to anti-PD-1 (100%) |
34.3% (G ≥3: 60.9%) |
3% | 11.9% |
| Mouri et al. [40] | 8 | Stage III/IV NSCLC | 21 (G ≥3: 33%) |
Resumption: anti-PD-1 (100%) |
71.4% (G ≥3: 6.7%) |
NR | NR |
| Pollack et al. [41] | 7 | Metastatic melanoma | 80 (G ≥3: 69%) |
Resumption: Anti-PD-1 (100%) |
50% (G ≥3: 35%) |
17.5% (G ≥3: 50%) |
30% |
| Patrinely et al. [29] ‡ | 8 | Melanoma (84%) ¶ Lung (7%) ¶ RCC (3%) ¶ Squamous cell (1.2%) ¶ Other (4%)¶ |
66 (G ≥3: 39%) |
NR | 39.4% | 25.8% (G ≥3: 41.2%) |
NR |
| Ravi et al. [44] | 6 | RCC | 69 (G ≥3: 26%) |
Switch or resumption (no details on ICI) |
44.9% (G ≥3: 35.5%) |
NR | NR |
| Santini et al. [42] | 7 | NSCLC | 38 (G ≥3: 34%) |
Resumption: Anti-PD(L)-1 to anti-PDL-1 (63%) Anti-PD(L)-1 + anti-CTLA-4 to anti-PDL-1 (37%) |
52.6% (G ≥3: 40%) |
26.3% (G ≥3: 60%) |
5.2% treatment-related death |
| Simonaggio et al. [43] | 6 | Melanoma (28%) Lung (15%) Lymphoma (15%) Colorectal (15%) Other (30%) |
40 (G ≥3: 55%) |
Resumption: Anti-PD(L)-1 (100%) |
55% (G ≥3: 61.9%) |
42.5% | NR |
* Among the 27 patients with grade ≥3 irAEs (no data available on the 31 patients with grade 1–2 irAEs); † Focus only on ICI-related IMBC; †† Among the 138 patients with documented colitis; ††† Focus only on ICI-related AKI; ¶ Among patients with overall irAE (no data available on the irAE rechallenged sub-group); ‡ Focus only on ICI-related hepatitis; AKI: Acute kidney injury; CTLA-4: cytotoxic T-lymphocyte antigen 4; irAE: immune-related adverse event; G: grade; NSCLC: non-small-cell lung cancer; IMDC: immune-mediated diarrhea and colitis; NOS: Newcastle Ottawa Scale; PD(L)-1: programmed cell death protein(ligand)- 1; NR: not reported; RCC: renal cell cancer; SCLC: small-cell lung cancer.