Major Research Findings

Ipilimumab is an immune checkpoint inhibitor used to treat cancers such as malignant melanoma. 5 indicates that the prognosis for metastatic melanoma is still limited. 1 reports that combination therapy with ipilimumab and nivolumab can cause uveitis resembling Vogt-Koyanagi-Harada (VKH) disease. 3 suggests that immune checkpoint inhibitors, including ipilimumab, may cause graft-versus-host disease (GVHD) in patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). 4 shows that uveitis can be rarely induced by biological agents used in cancer therapy, reporting on various biological agents including ipilimumab and nivolumab. 2 is a study investigating the safety of COVID-19 vaccines in skin cancer patients receiving immune checkpoint inhibitors, showing that grade 3 immune-related adverse events (irAEs) are reported more frequently in patients receiving combination therapy with nivolumab and ipilimumab.

Reasons for Side Effects

Immune checkpoint inhibitors, including ipilimumab, activate the immune system to attack cancer cells. However, this activation of the immune system can also target normal tissues and organs, leading to side effects. 1 suggests that ipilimumab may cause uveitis resembling VKH disease due to activation of the immune system. 3 suggests that immune checkpoint inhibitors, including ipilimumab, may cause GVHD. This is because ipilimumab may exacerbate the graft-versus-host reaction.

Common Side Effects

Uveitis

Combination therapy with ipilimumab and nivolumab has been reported to cause uveitis resembling VKH disease. 1 This side effect can recur even after treatment is stopped and can cause serious complications such as vision loss. 1

Graft-versus-host disease

Immune checkpoint inhibitors, including ipilimumab, have been reported to cause graft-versus-host disease (GVHD) in patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). 3 This side effect may be due to the potential of immune checkpoint inhibitors to worsen the graft-versus-host reaction. 3

Other Side Effects

Ipilimumab can cause other side effects. 4 These side effects include fatigue, rash, digestive problems, liver abnormalities, and more. 4 2 indicates that in skin cancer patients receiving ipilimumab who are vaccinated against COVID-19, common side effects such as pain at the injection site and fatigue are reported along with grade 3 immune-related adverse events (irAEs). 2

Measures to Counter Side Effects

Uveitis

If uveitis is suspected after ipilimumab administration, it is treated with anti-inflammatory drugs such as steroids. 1 Early initiation of treatment can prevent serious complications such as vision loss. 1

Graft-versus-host disease

If GVHD is suspected after ipilimumab administration, it is treated with immunosuppressants such as steroids. 3

Other Side Effects

Other side effects of ipilimumab are treated according to the symptoms. 4

Comparison between Studies

Commonalities

These studies suggest that immune checkpoint inhibitors, including ipilimumab, can cause serious side effects. 5 1 3 4 2

Differences

These studies suggest that the type and severity of ipilimumab side effects may vary depending on the patient and treatment regimen. 5 1 3 4 2 For example, 1 reports that combination therapy with ipilimumab and nivolumab can cause uveitis resembling VKH disease, while other studies do not report this side effect. 3 reports that immune checkpoint inhibitors, including ipilimumab, may cause GVHD, while other studies do not report this side effect. 4 shows that uveitis can be rarely induced by various biological agents, but it is not a study focused on ipilimumab side effects. 2 is a study investigating the safety of COVID-19 vaccines in skin cancer patients receiving immune checkpoint inhibitors, showing that grade 3 immune-related adverse events (irAEs) are reported more frequently in patients receiving combination therapy with nivolumab and ipilimumab. 2

Cautions Regarding Application in Real Life

Ipilimumab is an effective drug for treating cancers such as malignant melanoma, but it carries the risk of side effects. 5 When considering ipilimumab administration, it is necessary to carefully consult with a doctor to weigh the benefits and risks. 5 If you are receiving ipilimumab, it is important to be aware of side effects and consult your doctor early. 1 3 4 2

Limitations of Current Research

Research on ipilimumab side effects is still insufficient. 5 1 3 4 2 More research is needed to further investigate the side effects of ipilimumab. 5 1 3 4 2

Future Research Directions

To gain a deeper understanding of ipilimumab side effects, the following research is needed. 5 1 3 4 2

• Research to clarify the mechanisms by which ipilimumab causes side effects
• Research to develop biomarkers for predicting ipilimumab side effects
• Research to develop new treatments to reduce ipilimumab side effects

Conclusion

Ipilimumab is an effective drug for treating cancers such as malignant melanoma, but it carries the risk of side effects. 5 When considering ipilimumab administration, it is necessary to carefully consult with a doctor to weigh the benefits and risks. 5 If you are receiving ipilimumab, it is important to be aware of side effects and consult your doctor early. 1 3 4 2