Chronic granulomatous dermatitis induced by talimogene laherparepvec therapy of melanoma metastases

Abstract

Talimogene laherparepvec (TVEC) is the first oncolytic viral immunotherapy approved by the FDA, for advanced melanoma consisting of genetically modified herpes simplex type 1 virus which selectively replicates causing tumor lysis, expressing granulocyte macrophage‐colony stimulating factor (GM‐CSF) and activating dendritic cells. Intratumoral injection of TVEC produces objective response in 41% of stage IIB‐IV M1a melanoma. However, clinical response assessment can be problematic due to immune‐related inflammation at established tumor sites. Herein, we report 5 cases of granulomatous dermatitis developing at sites of TVEC injection associated with pathologic complete response in 4 of 5 patients. Over 5 months, TVEC injections were administrated in a median of 20 tumors per patient for 9 median doses prior to biopsy of persistent, indurated nodules. Granulomatous dermatitis with melanophages and melanin pigment incontinence was observed in all samples without evidence of melanoma cells in 4 patients. The fifth patient was rendered melanoma‐free by resection of the 1 nodule out of 4 with persistent tumor. Repetitive administration of TVEC or other oncolytic viral immunotherapies mimicking unresolved infection can produce granulomatous inflammation confounding assessment of the degree of tumor response and need for additional TVEC therapy. Tumor biopsies are encouraged after 4 to 6 months of TVEC administration to differentiate melanoma from granulomatous inflammation. Patients with confirmed granulomatous dermatitis replace continued with remained in remission after treatment discontinuation. Inflammatory nodules typically regress spontaneously.

Panniculitis in a patient with pathologic complete response to talimogene laherparepvec treatment for recurrent, in‐transit melanoma

“…Granulomatous dermatitis has been reported in association with T‐VEC in a series of five cases . Four of five achieved complete pathologic response, and one showed partial response.…”

“…Reported irAEs include vitiligo, pneumonitis, vasculitis, glomerulonephritis, and worsening of psoriasis . Neutrophilic dermatitis and granulomatous dermatitis have also been reported . We report a case of histopathologic panniculitis occurring in the setting of T‐VEC injection.…”

“…2 Neutrophilic dermatitis and granulomatous dermatitis have also been reported. 9,10 We report a case of histopathologic panniculitis occurring in the setting of T-VEC injection. To our knowledge, histologic panniculitis has not been previously reported with T-VEC therapy.…”

The histological spectrum of talimogene laherparepvec (TVEC) injections—Neutrophilic and chronic granulomatous dermatitis

“…Our series showed complete response under treatment with an average of 6.5 injections (range: 4‐9). This is less than the average of 9.8 injections (range: 7‐15) administered by Everett et al Granulomatous findings were subtle in a number of cases, with overall fewer injections and shorter treatment time prior to biopsy collection compared to Everett et al…”

“…We read with interest the case series by Everett et al describing chronic granulomatous dermatitis at sites of talimogene laherparepvec (TVEC) injections for advanced melanoma. We would like to report three additional cases with a total of six biopsy sites (Table ).…”