Table 3.
Emerging and potential future therapies for immune adverse events associated with immune checkpoint inhibitors.
| Drug | Mechanism of action | Efficacy in reversing irAE | Effect on tumor response | Clinical trial |
|---|---|---|---|---|
| Vedolizumab | Anti-integrin α4β7 mAb | Colitis (137, 248). Prevention of autoimmune flares in patients with IBD (249). |
Favorable clinical outcomes (248, 249). |
NCT04407247: Comparison of vedolizumab versus infliximab for clinical response of ICI-induced diarrhea/colitis. NCT04797325: Comparison of vedolizumab versus prednisolone for clinical response of ICI-induced colitis. |
| Alemtuzumab | CD52 mAb | Myocarditis (198). | Unknown | |
| Abatacept | CTLA-4 agonist | Myocarditis (250). | Unknown | |
| Rituximab | Anti-CD20 mAb | Neurological complications (e.g., encephalitis and myasthenia gravis), bullous pemphigoid-like skin disease, renal vasculitis, hematological complications (12, 175, 204, 251–253). | Progression, partial and complete responses reported (251–253). | NCT03719131: Evaluation of rituximab on ICI-induced irAEs. |
| Tocilizumab | Anti-IL-6 receptor mAb | Pneumonitis, colitis, and pancreatitis (254). Inflammatory arthritis (255). |
Clinical improvement with trend towards worse survival with increased doses of tocilizumab (254). 1/3 patients maintained anti-tumor response (255). |
NCT03999749: Evaluation of tocilizumab on diarrhea and/or colitis and/or arthritis induced by ICIs. NCT04691817: Evaluation of tocilizumab on irAEs in patients with non-small lung cancer (NSCLC) treated with atezolizumab. |
| Secukinumab | Anti-IL-17A mAb | Psoriatic rash and colitis (256). Psoriasiform dermatological complication (257). |
Tumor progression occurred in one patient (256). No impact on tumor response (257). | |
| Anakinra | IL-1 receptor antagonist | Experimental intestinal inflammation associated with combined immune checkpoint blockade in mice (96). | Unknown |
NCT04576429: Evaluation of anakinra on irAEs and cytokine profile in patients with different cancers. |
| Fecal microbiota transplant | Possibly increased Tregs and decreased effector T cells (258). | Colitis (258). | Unknown |
NCT04038619: Phase I trial of fecal microbiota transplant (FMT) for ICI-induced colitis/diarrhea. NCT04163289: Prevention of irAEs using fecal microbiota transplant. NCT03819296: Prevention of gastrointestinal irAEs by FMT in patients with melanoma or genitourinary cancer. |
| Certolizumab | anti-TNF-α |
NCT03293784: Comparison of infliximab or certolizumab + nivolumab + ipilimumab in patients with melanoma. |
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| Intravenous immunoglobulin (IVIG) |
NCT04438382: Comparison of infliximab versus IVIG in patients with pneumonitis. |