Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Objective: The use of immune checkpoint inhibitors (ICI) in immunosuppressed patients with cutaneous squamous cell carcinoma (cSCC) is limited, as initial ICI clinical trials excluded this at-risk population. Our objective is to provide a state of art review defining the feasibility of ICI in immunosuppressed patients with head & neck (HN) cSCC.
Method: A structure literature search was performed querying 3 databases (Pubmed, Embase, Ovid) from January 1st, 2019 to December 31st, 2024. Search terms included: immunotherapy, cemiplimab, pembrolizumab, PD-1, PD-L1, cutaneous squamous cell carcinoma, immunosuppression, transplant. Inclusion criteria was patients with HN cSCC, actively immunosuppressed, and treated with ICI. Demographic data was collected to include age, gender, immunosuppression etiology, and use of treatment prophylaxis. Outcomes of interest included overall response rate (ORR) and organ transplant rejection.
Results: A total of 13 studies met inclusion criteria: 8 individual case reports and 5 case series. Overall, 22 patients were identified:20 [91%] male; mean age 68 ± 12 years [SD]. Immune checkpoint inhibitors included: 12 cemiplimab, 9 pembrolizumab, 1 both. Immunosuppression included: 17 solid organ transplant (SOT) patients (14 kidney, 2 liver, 1 lung), 4 lymphoproliferative disorders, and 1 patient with human immunodeficiency virus. Eight of the 17 SOT patients were on mammalian target of rapamycin (mTOR) inhibitors. Steroid prophylaxis was the most common strategy to reduce adverse ICI effects to include organ rejection; there were no set protocol for prophylactic steroid dosing. The ICI overall response rate (ORR) was 63.6%; steroid use was not associated with decreased ORR. Of the 17 SOT patients, 4 received prophylactic high dose steroids or had an increase in baseline steroid dosing; none had ICI related organ rejection. 3 of 17 (17.7%) SOT patients experienced organ rejection; all had kidney transplants. With respect to lymphoproliferative disorders: 2 patients with myelofibrosis on JAK inhibitors experienced complete ICI response without associated sequela; 2 patients experienced CLL progression while on ICI; 1 patient with HIV had a partial cSCC response without detriment.
Conclusion: While ICI is contraindicated in immunosuppressed HN cSCC patients, this state of the art review identified 22 HN cSCC patients (17 SOT) treated. The ORR of 63.6% is reported, comparable efficacy in immunocompetent individuals. Care must be taken in this population for risk of immune related adverse events, and in SOT, the risk of organ transplant rejection was reported to be 17.7%. Future prospective trials may better elucidate efficacy and safety of ICI in immunosuppressed cSCC patients.