Recently, Allison and Honjo have been awarded with the Nobel prize for their findings leading to the new cancer treatment approaches known as immune checkpoint inhibitors (ICIs). Thanks to these discoveries in fact, the management of the disease has profoundly changed, producing remarkable results on several tumors, even if checkpoint inhibitors have significant side effects, that according to an analysis published in Jama are still poorly known by many health professionals. It is “urgent”, according to authors, “to identify who is at highest risk of severe outcomes, and then develop evidence-based therapies to manage toxicity”.
Understanding these adverse effects is essential not for oncologist only, but for every physician in any discipline, as said by Douglas B. Johnson, MD, of Vanderbilt University, Nashville, Tennessee, and colleagues. Indeed, they underlined what are the most common effects which occur in practice in an article published online in JAMA.Many organs can be involved, commonly the skin, the gastrointestinal tract, the lungs, endocrine organs, musculoskeletal, renal, nervous, hematologic, cardiovascular, and ocular systems, thus counting such side effects as a problem to be faced jointly among the various physicians.
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.
Their conclusion is clear: “ICIs are progressively prescribed more and more for patients with metastatic cancer since they can accomplish long-lasting responses to treatment, but because checkpoint inhibitors have only been commercially available since 2011, long-term adverse events have not been characterized yet. It’s therefore urgent to identify who is at highest risk of severe outcomes, and then develop evidence-based therapies to manage toxicity”.