Four cases of disseminated herpes simplex virus following talimogene laherparepvec injections for unresectable metastatic melanoma.

To the Editor: In the article titled “Durable melanoma control following disseminated talimogene laherparepvec herpetic infection,” Shmuylovich et al1Shmuylovich L. McEvoy A.M. Fields R.C. Hernandez-Aya L. Ansstas G. Chen D.Y. Durable melanoma control following disseminated talimogene laherparepvec herpetic infection.JAAD Case Rep. 2022; 29: 131-133https://doi.org/10.1016/j.jdcr.2022.09.012Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar presented a case of disseminated herpes simplex virus (HSV) following talimogene laherparepvec (T-VEC) intralesional therapy for unresectable locally advanced melanoma. We are aware of 1 other published case by Kimmis et al.2Kimmis B.D. Luu Y. Dai H. Disseminated herpes infection following talimogene laherparepvec administration.JAMA Dermatol. 2022; 158: 456-457Crossref PubMed Scopus (2) Google Scholar Here, we describe 4 additional cases of disseminated HSV in immunocompetent patients following T-VEC therapy. The patients consented to having nonidentifying photographs taken and utilized for educational and research purposes as well as sharing of descriptions of their cases and nonidentifying information. A 76-year-old man with American Joint Committee on Cancer Stage III C3 melanoma of the upper portion of the right arm was treated with 1.2 mL of 106-plaque-forming units (PFU)/mL T-VEC divided among 4 in-transit lesions. On postinjection day (PID) 10, vesicles developed on the right side of the chest, right axilla, and right arm (Fig 1). Although both punch biopsies taken yielded negative results for HSV 1 and 2, as determined using immunohistochemistry, a diagnosis of HSV infection was made based on the pattern of inflammation and epidermal necrosis (Fig 2) and a positive result of polymerase chain reaction for vesicular fluid HSV. T-VEC was discontinued, and a 10-day course of valacyclovir resolved the rash.Fig 2Case 1. A punch biopsy showing epidermal necrosis, vesiculation, and superficial lymphocytic infiltrate. (A and B, Hematoxylin-eosin stain; A, low power; B, high power.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) A 67-year-old man with stage IIID3Amin M.B. Greene F.L. Byrd D.R. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing: American Joint Commission on Cancer, 2017Crossref Google Scholar melanoma of the right heel was treated with 0.5 mL of 106-PFU/mL T-VEC divided among 24 in-transit lesions. On PID 1, he developed fever, arthralgias, and fatigue. On PID 7, he developed a nontender, nonpruritic, vesicular rash extending beyond the injection sites. On PID 8 (Fig 3), 1 of 2 biopsied lesions was HSV positive, as determined using immunohistochemistry (Fig Y). T-VEC was discontinued, and a 10-day course of valacyclovir resolved the rash. A 79-year-old man with stage IIIC3Amin M.B. Greene F.L. Byrd D.R. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing: American Joint Commission on Cancer, 2017Crossref Google Scholar melanoma of the right plantar foot was treated with 0.3 mL of 106-PFU/mL T-VEC divided among 3 in-transit lesions. On PID 3, he developed diffuse, mild erythema and fever, which progressed by PID 4 to a nonpruritic, nontender, and nonexudative violaceous eruption extending to the thigh. On PID 8, the patient presented with crusted, grouped erythematous papules (Fig 4); a punch biopsy yielded a positive result for HSV, as determined using immunohistochemistry. T-VEC was discontinued, and a 10-day course of valacyclovir resolved the rash. A 73-year-old man with stage III3Amin M.B. Greene F.L. Byrd D.R. AJCC Cancer Staging Manual. 8th ed. Springer International Publishing: American Joint Commission on Cancer, 2017Crossref Google Scholar melanoma of the left calf was treated with 0.5 mL of T-VEC at 106 PFU/mL in a region of subcutaneous metastasis of the left thigh. Between PIDs 7 and 8, he reported arthralgias, myalgia, fever, generalized weakness, severe fatigue, dyspnea, an injection-site vesicular rash, altered mentation, and imbalance requiring admission to the intensive care unit. Empiric intravenous acyclovir and broad-spectrum antibiotics were initiated, and polymerase chain reaction test of cerebral spinal fluid ultimately returned a positive result for HSV-1. A 3-week course of intravenous acyclovir and physical therapy resolved all symptoms. T-VEC was discontinued. Our patients had no known immunocompromising factors or history of HSV infection and only received the initial 106-PFU/mL dose of T-VEC. Two cases had received prednisone; however, T-VEC was initiated more than 1 month after prednisone discontinuation. Both the case described by Kimmis et al2Kimmis B.D. Luu Y. Dai H. Disseminated herpes infection following talimogene laherparepvec administration.JAMA Dermatol. 2022; 158: 456-457Crossref PubMed Scopus (2) Google Scholar and our case had received prior immune checkpoint inhibitor treatment.2Kimmis B.D. Luu Y. Dai H. Disseminated herpes infection following talimogene laherparepvec administration.JAMA Dermatol. 2022; 158: 456-457Crossref PubMed Scopus (2) Google Scholar Although it is possible that immune checkpoint inhibitors are associated with an increased risk of disseminated HSV, our patients had discontinued immune checkpoint inhibitors over 3 months prior to T-VEC treatment.