Table 2.
Overcoming severe irAEs and toxicity:
| Drug combination | Target | Mechanism/Rational | Outcomes | Indications | Reference |
|---|---|---|---|---|---|
|
ICI
anti-TNFα agents |
PD-1, PD-L1, CTLA-4 TNFα |
TNFα is a potent pro-inflammatory cytokine that play an important role in the pathogenesis of chronic inflammatory diseases, such as colitis and arthritis. | Success in managing the inflammation and alleviating symptoms | Corticosteroid-refractory ICI-induced polyarthritis and ICI-induced colitis | 78, 79 |
|
ICI
Anakinra or Canakinumab |
PD-1, PD-L1, CTLA-4 IL-1 |
IL-1 inhibition is beneficial in ICI-related irAEs due to its prominent role in acute inflammation, with no negative impact on cancer response. | Alleviation of disease symptoms | Myasthenia gravis, encephalitis, severe arthritis, and psoriasis | 80, 81 |
|
ICI
Tocilizumab |
PD-1, PD-L1, CTLA-4 IL-6 |
Aside from the anti-inflammatory benefits, IL-6 is also known to promote cancer development and metastasis. Thus, by targeting IL-6 while treating with ICI, a synergistic effect could be achieved | Alleviation of disease symptoms | Severe arthritis, uveitis, graves' orbitopathy, myocarditis, large-vessel vasculitis, severe pneumonitis, and myasthenia gravis | 82, 83, 84, 85, 86 |
|
ICI
Rituximab |
PD-1, PD-L1, CTLA-4 CD20 |
ICI-related encephalitis is associated with the presence of anti-neural autoantibodies | Impressive neurological improvement in patients with ICI-related encephalitis | ICI-related encephalitis | 87, 88, 89, 90, 91 |
|
ICI
IVIG |
PD-1, PD-L1, CTLA-4 Various components of the immune system |
Neutralization of pathogenic autoantibodies, prevention of B-cells proliferation, suppression of pro-inflammatory cytokines production | Alleviation of disease symptoms | Pre-existing paraneoplastic neuromuscular diseases in cancer patients, corticosteroids-refractory immune thrombocytopenia | 92, 93 |
Abbreviations: ICI immune checkpoint inhibitor, PD-1 programmed cell death protein 1, PD-L1 programmed death-ligand 1, CTLA-4 cytotoxic-T-lymphocyte-associated protein 4, TNFɑ tumor necrosis factor alpha, IL-1 Interleukin-1, IL-6 Interleukin-6, IVIG intravenous immunoglobulin.