Major research findings

Ipilimumab, an anti-CTLA4 therapy, is widely used for various cancers. However, it can cause immune-related adverse effects throughout the body, including the eye. 2 investigated whether ipilimumab induces retinal and choroidal abnormalities in rodents and explored potential underlying mechanisms. The results showed that ipilimumab may lead to outer photoreceptor architecture impairments accompanied by CD8-positive infiltration in the retina and CD45-positive cell infiltration in the choroid, potentially contributing to retinal function deterioration. 8 aimed to assess the safety of COVID-19 vaccines approved in Germany for skin cancer patients receiving immune-checkpoint inhibitor treatment. The study indicated that approved COVID-19 vaccinations are safe for use in cancer patients receiving ICIs, but some precautions should be taken, especially concerning the timing of vaccination and ICI treatment. 3 reported the results of a Phase 1b study evaluating V937 in combination with ipilimumab for patients with uveal melanoma. While the combination showed a manageable safety profile, it didn't offer meaningful clinical benefit for patients with uveal melanoma and liver metastases. 10 explored the safety and efficacy of combining UV1, a universal telomerase-based cancer vaccine, with ipilimumab for metastatic melanoma. The trial indicated that this combination was safe and showed efficacy in some patients. 12 reviewed clinical and molecular insights into BCG immunotherapy for melanoma. The review highlighted BCG's role as a strong immune modulator, inducing the recruitment of various immune cells, making it a potentially effective treatment for melanoma. 5 presented a case report of a non-small cell lung cancer patient experiencing cytokine release syndrome (CRS) after vaccination with mRNA-1273 while on ipilimumab and nivolumab maintenance therapy. This case suggests that repeated vaccinations might contribute to the development of CRS in patients receiving ICIs. 4 reviewed treatment options and novel drug delivery systems for melanoma. The review highlighted the various treatments for melanoma, including surgery, chemotherapy, immunotherapy, radiation therapy, and targeted therapy, and the emerging potential of advanced delivery systems like nanoparticles and liposomes. 7 reported a case of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis after resuming nivolumab and ipilimumab. This case emphasizes the importance of monitoring for VKH disease-like uveitis recurrence during ICI administration, even after initial treatment. 9 presented a case of fulminant type 1 diabetes mellitus developing about half a year after discontinuation of nivolumab and ipilimumab combination therapy. This case highlights the potential for delayed immune-related adverse events (irAEs) even after ICI discontinuation, requiring ongoing monitoring. 6 summarized 8 cases of melanoma with ICI-induced type 1 diabetes and discussed clinical features and risk factors. The review showed that ICI can lead to type 1 diabetes and highlights the need for monitoring. 1 reported bilateral hypotony maculopathy unresponsive to corticosteroid treatment following ipilimumab and nivolumab therapy, emphasizing the need to further explore the mechanisms behind ICI-associated hypotony. 11 described a rare case of panuveitis during ipilimumab and nivolumab combination treatment for small-cell lung cancer, highlighting the potential for immune-related ocular toxicities during ICI treatment, requiring prompt recognition and management by healthcare providers.

Benefits and Risks

Benefit Summary

Ipilimumab holds potential for extending survival and reducing tumor size in certain cancer patients. 10 showed that combining ipilimumab with a cancer vaccine extended survival in some metastatic melanoma patients. 12 suggested that BCG immunotherapy is effective in treating metastatic melanoma. 8 investigated the safety of COVID-19 vaccines for skin cancer patients receiving immune-checkpoint inhibitors and suggested that the vaccines are safe.

Risk Summary

Ipilimumab can trigger immune-related adverse effects throughout the body, including the eye. 2 demonstrated that ipilimumab can cause abnormalities in the retina and choroid of rodents, specifically outer photoreceptor architecture impairments, CD8-positive infiltration in the retina, and CD45-positive cell infiltration in the choroid, leading to potential retinal function deterioration. Additional immune-related adverse effects from ipilimumab include diarrhea, fatigue, and muscle aches. 3 reported immune-related adverse effects like diarrhea, fatigue, and myalgia in patients receiving ipilimumab and V937. 6 highlighted the possibility of immune-checkpoint inhibitors inducing type 1 diabetes. 9 reported a case of fulminant type 1 diabetes developing after discontinuing ipilimumab and nivolumab, highlighting the potential for delayed irAEs. 5 showed a case of CRS in a patient receiving ipilimumab and nivolumab after mRNA-1273 vaccination, suggesting repeated vaccinations might contribute to CRS in patients on ICIs.

Comparison across Studies

Commonalities

These studies consistently highlight that immune-checkpoint inhibitors, such as ipilimumab, offer potential benefits for cancer treatment but can also induce immune-related adverse effects. These studies emphasize the need for further research into the safety and efficacy of these therapies.

Differences

The studies differ in the type of cancer, ipilimumab administration method, other medications used alongside ipilimumab, and types of immune-related adverse effects observed. For instance, 2 focused on the retinal and choroidal effects of ipilimumab in rodents, while 8 assessed COVID-19 vaccine safety in skin cancer patients on ICIs. 3 evaluated a combination therapy of ipilimumab and V937 for uveal melanoma.

Consistency and Discrepancies in Findings

These studies show that ipilimumab can be beneficial for cancer treatment but also carries the risk of immune-related adverse effects. However, the specific mechanisms of action and the factors influencing the development of adverse effects in different patient populations require further investigation. Additionally, variations in research designs make comparing results across studies challenging.

Considerations for Real-World Applications

While ipilimumab and other immune-checkpoint inhibitors show promise in cancer treatment, their use should be approached with caution. Patients and healthcare providers must remain vigilant for immune-related adverse effects and seek prompt medical attention if they arise. It's essential to consult with a doctor to discuss the potential benefits and risks of ipilimumab treatment and to select the most appropriate treatment plan for each individual.

Limitations of Current Research

The studies provide limited data on the long-term effects and safety of ipilimumab. Furthermore, these studies often focus on specific cancer types or patient groups, making it challenging to generalize their findings.

Future Research Directions

Future research should delve deeper into the long-term effects and safety of ipilimumab. Understanding its specific mechanisms of action and identifying factors that make certain individuals more susceptible to immune-related adverse effects is crucial. Developing novel treatment and prevention strategies to mitigate side effects is also essential.

Conclusion

Ipilimumab holds potential for improving survival and shrinking tumors in some cancer patients. However, it carries the risk of causing immune-related adverse effects throughout the body, including the eye. It is essential to be aware of these risks and to seek prompt medical attention if adverse effects occur. While ipilimumab shows potential in cancer treatment, further research is needed to fully understand its safety and efficacy.