Systemic Therapies for the Treatment of Cutaneous Malignancies in Solid Organ Transplant Recipients

BACKGROUND: Solid organ transplant recipients (SOTRs) face frequent advanced cutaneous malignancies, yet data guiding systemic therapy are limited. MATERIALS AND METHODS: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review of immune checkpoint inhibitors (ICIs), talimogene laherparepvec (T-VEC), and Sonic Hedgehog Pathway Inhibitors (HPIs) for locally advanced or metastatic cutaneous squamous cell carcinoma, melanoma, Merkel cell carcinoma, and basal cell carcinoma in SOTRs, including a novel case from our institution. Outcomes included tumor response, graft rejection, and graft failure. RESULTS: Among 196 SOTRs treated with ICIs (101 cutaneous squamous cell carcinoma, 83 melanoma, 12 Merkel cell carcinoma), the overall response rate (ORR) was 39.3%, and lack of progression occurred in 58.0%. Graft rejection occurred in 36.9% and graft failure in 22.3%. A higher number of baseline immunosuppressive agents decreased odds of rejection (OR 0.55) and failure (OR 0.38). Tacrolimus was associated with reduced tumor response (OR 0.41), whereas mTOR-based regimens and cemiplimab were associated with fewer transplant rejection. T-VEC was reported in 10 SOTRs with an ORR of 90% and no graft rejection or failure. HPIs in six SOTRs with basal cell carcinoma demonstrated ORR of 83% without graft loss. CONCLUSION: ICIs provide antitumor activity but substantial graft-related risk, while T-VEC and HPIs show high response rates with no reported rejection.