Interleukin-2 improves tumour response to DNP-modified autologous vaccine for the treatment of metastatic malignant melanoma

Abstract

This paper is a report of response rate (RR) and survival of 34 metastatic melanoma patients who received a dinitrophenyl (DNP)-modified autologous melanoma cell vaccine. In all, 27 patients started the vaccine as a primary treatment for metastatic melanoma and seven started it as an adjuvant, with no evidence of disease at the time, but had developed new metastases. Interleukin-2 (IL-2) was administered in 24 out of the 34 patients: 19 who progressed on vaccine alone and five who had the combination from start. Interleukin-2 was administered in the intravenous, bolus high-dose regimen (seven patients) or as subcutaneous (s.c.) low-dose treatment (17). Overall response for the entire group was 35% (12 patients out of 34), 12% having a complete response (CR) and 23% a partial response (PR). However, only two patients had tumour responses while on the vaccine alone, whereas the other 10 demonstrated objective tumour regression following the combination with IL-2 (two CR, eight PR), lasting for a median duration of 6 months (range 3-50 months). Of the 12 responding patients, 11 attained strong skin reactivity to the s.c. injection of irradiated, unmodified autologous melanoma cells. None of the patients with a negative reactivity experienced any tumour response. Patients with positive skin reactions survived longer (median survival - 54 months). The results suggest enhanced RRs to the combination of IL-2 and autologous melanoma vaccine. Skin reactivity to unmodified autologous melanoma cells may be a predictor of response and improved survival, and therefore a criterion for further pursuing of immunotherapeutic strategies.

Figure 1

Framework of treatment.

Figure 2

Kaplan–Meier survival curve as a function of DTH response to unmodified autologous tumour cells. Data available from 32 patients. DTH test was not performed for two patients with a rapidly progressing disease.

Figure 3

(A) Pelvic CT prior to initiation of low-dose IL-2, in a patient who received adjuvant autologous melanoma vaccine, and had recurrent pelvic LN metastases 12 months later (patient 3). (B) Partial regression of pelvic lymph nodes after 6 months of therapy.

Figure 4

(A) Regressing dermal metastases with perilesional vitiligo in patient 4. (B) Melanin-laden melanophages in upper dermis, in a skin biopsy from a regressing lesion of patient 4 (H&E × 20). (C) White hair arising from regressed s.c. metastases. Hair of noninvolved skin is fully melanised (patient 11).

Figure 5

Patient 9: CT of the thorax. (A and B). Three metastatic deposits <1 cm. (C and D). At 3 months after initiation of autologous melanoma vaccine with low dose and inhalations of IL-2–significant partial regression of all lesions. Patient has eventually achieved CR.