14937 Keratoacanthomas associated with anti–TGF-β immunotherapy

Abstract

Keratoacanthomas (KAs) are rapid-growing skin tumors that resemble well differentiated cutaneous squamous cell carcinomas (SCCs) and typically present as solitary lesions on sun-exposed skin. KAs can arise in association with medications, including inhibitors of BRAF or transforming growth factor beta (TGF-β). A novel bifunctional fusion protein that blocks both programmed death ligand 1 (PD-L1) and TGF-β signaling has shown a manageable safety profile and clinical efficacy in patients with heavily pretreated solid tumors. In these patients, we have observed adverse events (AEs) that include both immune-related AEs and biopsy-proven KAs. In total, 18 of 93 treated patients (19%) developed at least 1 KA. These lesions appeared on chronically sun-damaged skin, typically months after starting therapy. KA-like papules were managed by observation with destructive therapy (cryotherapy or excision) used for symptomatic or clinically atypical lesions. Patients generally did not require treatment discontinuation. Whereas most patients had small numbers of treatment-emergent KAs, 3 patients developed numerous eruptive KAs. These patients’ presentations resembled Grzybowski-type eruptive KAs in that they also demonstrated generalized pruritus, macular erythema, and/or lesions in areas of prior instrumentation suggestive of an isomorphic response. Acitretin was helpful in controlling the eruptive KAs and associated AEs. The occurrence of isolated and eruptive KAs in this patient population adds to a growing body of evidence supporting an association between KA development and reduced TGF-β signaling. Ongoing studies are investigating the predisposing genetic and molecular factors required for TGF-β inhibitor–related KAs and exploring strategies to prevent these cutaneous neoplasms.