Feasibility of Intratumoral Anti-PD1 as Treatment of Human Basal Cell Carcinoma: An Explorative Study with Adjuvant Ablative Fractional Laser

SIMPLE SUMMARY: The use of immune checkpoint inhibitors (ICI) is expanding with the approval for locally advanced and metastasizing keratinocyte carcinoma.

Most cases, however, are non-aggressive.

Systemic therapy remains limited by severe side effects.

Local administration could broaden ICI, but an adequate immune response might require an immune-attractive adjuvant such as ablative fractional laser (AFL).

Accordingly, aiming to broaden the field of ICI to keratinocyte carcinoma, this study investigates the intratumoral injection of anti-PD1 with and without AFL in basal cell carcinoma (BCC), exploring anti-PD1 concentration, immune cell infiltration, tumor response, and safety.

With the results of the study showing the feasibility of intratumoral anti-PD1 and increase in immune cell infiltration and tumor reduction upon combined anti-PD1 and AFL, local, hence broader, application of anti-PD1 holds potential for future treatment of non-aggressive keratinocyte carcinomas.

ABSTRACT: The use of immune checkpoint inhibitors (ICI) is expanding with the approval for advanced/metastatic keratinocyte carcinoma; however, most tumors are non-aggressive.

Local administration could broaden ICI, but adequate immune response might require an immune-attractive adjuvant such as ablative fractional laser (AFL).

Accordingly, this study aimed to explore intratumoral injection of anti-PD1 with and without AFL in basal cell carcinoma (BCC), exploring anti-PD1 concentration, immune cell infiltration, tumor response, and safety.

This open-label, proof-of-concept trial investigated intratumoral anti-PD1 + AFL combination therapy versus anti-PD1 or AFL monotherapy in 28 BCC patients.

The primary endpoints were immune cell infiltration evaluated immunohistochemically and clinical tumor response after 3 months.

The secondary outcomes were tumoral drug concentration and safety.

The most robust response was obtained following intervention with combined anti-PD1+AFL, leading to a ~2.5-fold increase in CD3+ cells (p = 0.027), and tumor reduction ≥25% in 73%, including two tumors with complete remission.

Upon anti-PD1 monotherapy, a slight decrease in CD3+ cells was observed while a non-significant increase following AFL was seen.

Tumor reduction ≥25% was seen in 45% and 50%, respectively, after anti-PD1 and AFL monotherapy.

The CD8/CD3 ratio remained unchanged after anti-PD1+AFL and anti-PD1 monotherapy, while AFL led to a decreased ratio.

A non-significant decline in the Foxp3/CD3 ratio was observed for all groups.

Side-effects were mild with no systemic drug concentration detected.

Intratumoral anti-PD1 injection is feasible, and a single exposure to locally injected anti-PD1 with adjuvant AFL increased immune cell infiltration and reduction in BCC with limited side-effects.