Autologous dendritic cell vaccine (ADCV) in combination with plasmapheresis (PP) and cyclophosphamide (Cy) in patients with disseminated melanoma: A phase II study.

Abstract

e13059 Background: Low immunogenicity of tumor-associated antigens, cellular and humoral immunosuppressive factors compromise adequate antitumor immune response development. We hypothesized that ADTV, PP and Cy can overcome these immune escape mechanisms by enhancing antigen presentation, suppressing T-regs and removal of various immunosuppressive substances, respectively (Nand S, 1997; Salem M, 2010). Methods: Ten pts (median age 47.3 (24-74)) with stage IV morphologically verified malignant melanoma were included in the study in 2010. All pts signed inform consent form, previously received systemic therapy and have no brain metastases. Pts received 3 procedures of middle-volume PP (removal of 10 ml/kg plasma) on days 1,3,5 of the first 4 cycles, Cy 300 mg IM on day 5 after PP, DCV in 4 intradermal injection of 5-20*106 mature DC on day 8 of 14-day cycle. Pts with no evidence of disease progression after 4 cycles received Cy and DCV without PP once in a month for 1 year and once in 3 month thereafter until disease progression. Primary endpoint was Progression Free Survival (PFS). Secondary endpoints were toxicity (per CTCAE), efficacy (per irRECIST) and immune response using ELISpot and whole cell Elisa tests. Median of patient’s observation was 231 days. Results: Ten pts received 73 (2-21) cycles of therapy. No gr. 4 AE or SAE occurred. One patient (1.4% of cycles) developed gr. 3 fever. Main gr. 1-2 toxicities were fever (34.2%), flu-like syndrome (17,8%) and PP-related reactions, such as citrate intoxication, nausea or hypotension (16,4%). One pt achieved PR (10%, 95% CI 0 - 35%) lasting 956+ days. Four pts (40%, 95% CI 13-70%) had SD for 168, 262, 417 and 454 days (3/4-stage M1c). Median PFS was 168 (95% CI 10-325) days. IFN-γ production increased in all patients irrespective of tumor response (p=0.017). All patients with clinical benefit showed increased production of tumor-specific IgG in whole cell ELYSA. Relative risk of disease progression was 6.0 (95% CI 1.003-35.9, p=0.023) in the absence of tumor-specific IgG production. Conclusions: ADCV with PP and C is well tolerated and shows significant immunological and clinical response in pretreated stage IV pts.