Immune checkpoint inhibitors (ICIs) have significantly changed the landscape of cancer care, improving outcomes for patients diagnosed with a variety of cancers, including lung cancer, melanoma, kidney cancer, gynecological cancers, colorectal cancer and triple-negative breast cancer. At the same time, an increase in troubling oral side effects has experts pushing for greater awareness, treatment management guidelines and more research to improve care for those on ICIs.
Alessandro Villa, DDS, MPH, Ph.D., chief of Oral Medicine, Oral Oncology and Dentistry at Baptist Health Miami Cancer Institute, is the first author of “Oral Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors: Call to Action.” The paper was published in February in JCO Oncology Practice, a journal of the American Society of Clinical Oncology (ASCO).
“Up to 8 percent of patients on ICIs experience oral immune-related adverse events (irAEs),” Dr. Villa says. “ICIs are a class of cancer immunotherapy drugs that block immune checkpoints such as PD-1, PD-L1 and CTLA-4, which tumors use to evade immune attack.” When the checkpoints are inhibited, T-cell activity is boosted, allowing the immune system to target and destroy cancer cells more effectively.
“While ICIs have revolutionized cancer treatment,” he adds, “oral irAEs impact quality of life, leading to pain, weight loss, dehydration and, in severe cases, the need for feeding tube placement or opioid analgesics.” Common irAEs include xerostomia and hyposalivation, dysgeusia and oral mucosal lesions.
Dr. Villa teamed up with Bryan Schneider, M.D., University of Michigan Health System, Douglas Peterson, DMD, Ph.D., School of Dental Medicine at UConn Health, and Christina Lacchetti, MHSc and Thomas Oliver, B.A., both with ASCO, to develop the Call to Action.
The group recommends close monitoring of patients on ICIs to minimize problems and to detect adverse events early. Although the evidence is out on methods to prevent risk, patients should be educated on the importance of good oral hygiene, regular dental check-ups before and during ICI therapy, hydration and the use of saliva substitutes, the avoidance of spicy, acidic or rough-textured foods and maintaining a healthy diet and active lifestyle when possible.
At Miami Cancer Institute, Dr. Villa says, oral medicine specialists, collaborating with oncologists, perform routine oral exams before and during ICI therapy, educate patients on symptoms and prevention, provide early intervention to prevent severe complications and manage oral irAEs with appropriate treatment.
The paper’s authors also suggest that healthcare providers follow grading criteria to help manage oral irAEs. Among the treatment strategies are:
- Using topical steroids and saliva substitutes for mild (Grade 1) cases.
- Prescribing high-potency topical steroids, possible systemic corticosteroids and sialologues for moderate (Grade 2) events.
- Suspending or discontinuing ICIs, systemic steroids and immunosuppressants for severe (Grades 3-4) cases.
The Call to Action pushes for more research to both better understand who is at high risk for developing irAEs and to help develop new treatment approaches.
“There is some promising research underway, but we need more studies, particularly in the areas of biomarkers to identify genetic, immunologic and inflammatory markers; AI-based risk-prediction models that analyze patient data; and patient-reported outcome measures,” Dr. Villa says.
Dr. Villa is optimistic that as the use of ICIs increases, the number of oral immune-related adverse events can be reduced and better managed. The publication states, “Continued pursuit of optimal preventive and treatment interventions for oral irAEs, centered in future clinical practice guidelines created by multidisciplinary experts from organizations including ASCO, is now both timely and essential.”
