Clinical effects of in situ photoimmunotherapy on late-stage melanoma patients: a preliminary study

Abstract

Metastatic melanoma is a skin cancer with poor prognosis. In situ photoimmunotherapy (ISPI) is a promising modality for the treatment of metastatic melanoma that combines local, selective photothermal therapy with immunological stimulation. A preliminary clinical study was conducted to evaluate the safety and therapeutic effects of ISPI for late-stage melanoma patients using imiquimod as the immune modifier. Eleven patients received ISPI in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. ISPI consisted of three main components applied directly to the cutaneous metastases: 1) local application of topical imiquimod; 2) injection of indocyanine green (ICG); and 3) an 805 nm laser for local irradiation. All patients completed at least one cycle of treatment. The most common adverse effects were rash and pruritus at the treatment sites. No grade 4 toxicity was observed. Complete response was observed in six patients. All lesions in the treatment area of the patients responded to ISPI, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%. This study demonstrates that ISPI with imiquimod is safe and well tolerated. The patient response rate is promising. ISPI can be easily applied on an outpatient basis and can be combined with other modalities to improve the therapeutic response of metastatic melanoma.

Figures

Figure 1

Kaplan-Meier plot of the probability of overall survival. Dotted lines are the 95% confidence interval (95% CI) bands. Solid dots at 20.6, 22.5, 38.7, 44.9 and 64.2 months denote times for the six patients who were still alive at the time of last follow-up. The median survival time could not be computed, because the survival distribution never fell below 50%. The probability of 12 month overall survival was 70%.

Figure 2

Photos of lesion of one patient with stage III C melanoma around the left ear treated by in situ photoimmunotherapy (ISPI). (A) Before ISPI, showing extensive acute radiation damage and numerous small black metastases. (B) Immediately after the first laser treatment in the second cycle of ISPI, bullae can be seen after laser treatment. (C) Immediately after the second laser treatment in the second cycle of ISPI. (D) All treatment-related ulcers have healed and the subject is free of clinically and radiologically detectable tumors after completion of three cycles of ISPI.

Figure 3

Treatment cycle of photothermal immunotherapy for late-stage melanoma patients. The six-week treatment cycle was carried out on a designated 200 cm2 area of skin and consisted of six weeks of topical imiquimod treatment started two weeks before the first laser treatment session. Two laser treatment sessions were performed for each treatment cycle at the beginnings of week 2 and 4. Additional treatment cycles were carried out in the same treatment area or in different areas, if the response to the treatment is not complete.