Background Talimogene laherparepvec (T-VEC) has become an increasingly popular treatment option for surgically non-resectable, recurrent melanoma based on its durable efficacy and safety profile. The complete response (CR) rate has been reported to be ~20% with a median of ~9 months to achieve it.^{1 2} Assessment of treatment response in those studies has predominantly relied on the clinical impression of the size and color of the lesions. However, in the real-world, decrease of tumor size often occurs rapidly within the first 2–3 months, while improvement of the pigmentation takes several more months. Such clinical observation of lasting pigmentation could be explained by tumoral melanosis – a histopathologic term referring to the presence of a melanophage-rich inflammatory infiltrate without remaining viable tumor cells.

Methods We hypothesized that residual pigmentation of stable melanoma lesions while on successful T-VEC treatment may represent tumoral melanosis. We also report practical information of such phenomenon including timeline and clinical features.

Results We report 6 cases of metastatic cutaneous melanoma treated with T-VEC with excellent pathologic responses. Biopsies of 5 cases were performed after observing variable clinical changes in the injected tumors, with some shrinking or becoming flat, while others grew or became raised. The range of time to biopsy was 4–23 months from the initial treatment date. Pathologic evaluation macular lesions demonstrated non-viable tumor tissue with tumoral melanosis in all cases. In an additional case, clinically increased size of the injected tumor prompted surgical excision, which similarly showed tumoral melanosis without viable tumor. Of note, while size of the tumor was increased, SUV max of the lesion decreased from prior assessment on PET-CT. No patient has developed regrowth or recurrent melanoma of the injected lesions to date (table 1).

Conclusions In patients receiving T-VEC treatment, pathologic CR may be achieved within the first 2–3 months, which precedes clinical improvement of pigmentation. To decrease unnecessary additional T-VEC treatment and assess the response correctly, serial biopsy of stable pigmented lesions should be considered to assess for the presence or absence of viable tumor.

Acknowledgements N/A

Trial Registration N/A

Ethics Approval IRB exempted for case report with no patient-identifiable information

Consent N/A

References

1. Harrington KJ, Andtbacka RH, Collichio F, et al. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial. Onco Targets Ther 2016;9:7081–7093.

2. Andtbacka RHI, Collichio F, Harrington KJ, et al. Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III–IV melanoma.