Allison and Honjo recently received the Nobel Prize for their discoveries that helped develop the breakthrough cancer therapies known as immune checkpoint inhibitors (ICIs). Even though checkpoint inhibitors have significant side effects that, according to an analysis published in Jama, are still poorly known by many health professionals, these discoveries have actually had a profound impact on how the disease is managed and produced remarkable results on a number of tumours. "To determine who is at highest risk of severe consequences, and then create evidence-based therapy to manage toxicity," state the authors, is "urgent."
According to Douglas B. Johnson, MD, of Vanderbilt University, Nashville, Tennessee, and colleagues, understanding these adverse effects is crucial for all doctors, not just oncologists. In a JAMA study published online, scientists did in fact highlight the consequences that happen most frequently in real-world settings. The skin, gastrointestinal tract, lungs, endocrine organs, musculoskeletal, renal, neurological, hematologic, cardiovascular, and ophthalmic systems are just a few of the organs that may be affected. As a result, these side effects are considered an issue that needs to be handled by a team of doctors.
Autoimmune events are generally dose-dependent with anti–CTLA-4 treatments, such as ipilimumab, while they are not with the anti–PD-1/PD-L1 drugs (nivolumab and pembrolizumab), which act on the programmed cell death pathway. Most effects are acute (colitis, pneumonitis, skin AEs etc.) and normally glucocorticoids are used to cure them, but in about 10% of patients, adverse events will persist after steroid treatment has ended, and about 5% of patients who are receiving anti-PD-1 monotherapy will need to be hospitalized, the authors noted. The combination of anti-CTLA-4/anti-PD-1 immunotherapies increases the risk for adverse events, and hospitalization may be required for up 36% of patients receiving this combination. Those patients who do not improve after 3 to 7 days of steroid therapy should be considered for disease-specific, second-line immunosuppression, such as with infliximab or mycophenolate mofetil, the authors wrote.
They draw the following, unambiguous, conclusion: "ICIs are increasingly prescribed for patients with metastatic cancer because they can achieve long-lasting responses to treatment, but because checkpoint inhibitors have only been commercially available since 2011, long-term adverse events have not yet been characterised. Therefore, it is crucial to determine who is most at risk for serious consequences and then to develop evidence-based therapy to manage toxicity".
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