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

Area of Science:

• Oncology
• Immunology
• Transplantation

Background:

• Solid organ transplant recipients (SOTRs) have a higher incidence of advanced cutaneous malignancies.
• Limited data exist on effective systemic therapies for these cancers in SOTRs.

Purpose of the Study:

• To systematically review the efficacy and safety of immune checkpoint inhibitors (ICIs), talimogene laherparepvec (T-VEC), and Hedgehog Pathway Inhibitors (HPIs) for advanced cutaneous malignancies in SOTRs.
• To evaluate outcomes including tumor response, graft rejection, and graft failure.

Main Methods:

• A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
• Inclusion of studies on ICIs, T-VEC, and HPIs for cutaneous squamous cell carcinoma, melanoma, Merkel cell carcinoma, and basal cell carcinoma in SOTRs.
• Analysis of tumor response rates, overall response rates (ORR), graft rejection, and graft failure.

Main Results:

• Among 196 SOTRs treated with ICIs, the ORR was 39.3%, with 36.9% experiencing graft rejection and 22.3% graft failure.
• Higher baseline immunosuppression correlated with decreased odds of rejection and graft failure.
• T-VEC (10 SOTRs) showed a 90% ORR with no graft complications; HPIs (6 SOTRs) demonstrated an 83% ORR without graft loss.

Conclusions:

• Immune checkpoint inhibitors (ICIs) demonstrate antitumor activity in SOTRs but pose significant risks of graft rejection and failure.
• Talimogene laherparepvec (T-VEC) and Hedgehog Pathway Inhibitors (HPIs) present promising alternatives with high response rates and a favorable safety profile regarding graft integrity.