PMC10172468_01
Representative clinical course of a case of a complete responder, patient #2. (A) Photo of primary lesion on day one of IL-2 treatment. (B) Photo of lesion following IL-2 monotherapy showing progression of lesions. (C) Photo of lesion on the day of BCG initiation, showing stable disease (D) PET-CT early on during IL-2 monotherapy showing extent of disease, with metastatic node highlighted. (E) PET-CT following treatment with IL-2 and one BCG treatment, showing metastasis. (F) Photo of the lesion following two BCG treatments, showing the typical ulceration seen with BCG injection. G. Photo of the treated area following treatment course, showing complete resolution. H. Post-treatment PET CT, showing reactive lymphadenopathy with no further evidence of metastatic disease and radiographic resolution of the cutaneous lesions.
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Soon thereafter, he developed multiple cutaneous lesions around the surgical scar ( Figure 3A ), with palpable clinical adenopathy and a positron emission tomography/computer tomography (PET-CT) scan that demonstrated metastatic disease to subcutaneous tissues and lymph nodes ( Figure 3D ). He was initially started on iIL2 monotherapy to the left arm lesions, and had six treatments approximately every two weeks, which initially was concerning for progressive disease ( Figure 3B ) but following six IL-2 treatments stabilized ( Figure 3C ). Figure 3E ). Following two BCG treatments, the typical ulceration that occurs with BCG injection was observed at the cutaneous site ( Figure 3F ). Following 13 iIL2 and 3 BCG treatments, the lesions on his left arm clinically resolved ( Figure 3G ), and his post-treatment PET-CT scan revealed near complete resolution in uninjected metastatic lesions, including the bony metastasis ( Figure 3H ).
PMC10172468_02
A representative case from a complete responder to intralesional IL-2 and BCG therapy. (A) Representative images of the treated lesion throughout IL-2 monotherapy treatment course. (B) PET-CT scan three years into IL-2 monotherapy showing new uptake among cutaneous lesions, signaling disease progression. (C) Representative image of the treated lesion following IL-2 and BCG treatment. (D) PET-CT scan after three BCG treatments showing regression of main lesions radiographically with new FDG uptake in distal lesions. (E) Representative image of the area after treatment, showing clinical resolution of BCG ulcers and in-transit metastasis. (F) Surveillance PET-CT two years post-treatment, showing no evidence of disease.
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He received biweekly iIL2 for four years, which caused an initial partial response and regression of lesions ( Figure 4A ). Unfortunately, he eventually experienced therapeutic escape and stable disease, followed by radiographic evidence of recurrence even on iIL2 ( Figure 4B ). In November 2016, in hopes of stimulating more robust immunity, intralesional BCG was added to the regimen, causing typical ulceration and a significant inflammatory response at the site of injection ( Figure 4C ). BCG treatments in total, there was clinical and radiological evidence of regression of larger sites of disease ( Figure 4D ). BCG was thus continued, and following treatment, there was no obvious clinical sign of disease ( Figure 4E ). A surveillance PET-CT two years after his last dose of BCG revealed radiological complete response with no evidence of disease ( Figure 4F ), and clinically, he remains disease free five years after treatment.
Punch biopsy of lesion following intralesional-IL-2 and BCG. (A) No evidence of residual melanoma, central necrosis and surrounding granulomatous reaction (low power) (B) Area of central necrosis (medium power) (C) Granulomatous reaction (medium power) (D) Granulomatous reaction (high power).
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Punch biopsies of the lesions taken after his last dose of BCG (August 2017) revealed no evidence of residual melanoma with only necrosis and granulomatous inflammation ( Figures 5A-D ).