Abstract 651: Safety and efficacy of pembrolizumab plus personal dendritic cell vaccines in elderly patients with metastatic melanoma
Authors: Chaitali S. Nangia, Katrina L. Lopez, Gabriel I. Nistor, Robert O. Dillman
Journal: Cancer Research (2025)

Monoclonal antibodies targeting programmed death molecule-1 (anti-PD-1) are an effective immunotherapy for advanced melanoma. An investigational approach that has also produced encouraging long-term survival results in such patients is a patient-specific therapeutic vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) from autologous tumor cells that are self-renewing in tissue culture. There is a strong rationale for combining these two immunotherapy approaches, but the first step is establishing that it is safe to give both therapies concurrently. Eligible patients had advanced melanoma with at least one resectable lesion and were intended to be treated with an anti-PD-1 monoclonal antibody. There was no upper age limit. Co-administration of anti-CTLA-4 antibody was not allowed. Surgically resected metastatic melanoma tissue was processed into cell suspension, then cultured in liquid media that favors stem cell survival and progenitor cell proliferation. Lysates of Irradiated tumor cells (ITC) were used as ATA. Peripheral blood mononuclear cells were collected by leukapheresis, enriched for monocytes (MC), and then immature DC were differentiated from MC by culturing with granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-4. Antigen loading was accomplished by incubating DC with ITC lysate. During the 8 to 9 weeks while DC-ATA was being manufactured, patients received standard infusions of anti-PD-1. Over the next 24 weeks, anti-PD-1 was infused at standard intervals, and DC-ATA admixed in GM-CSF was injected s.c. at weeks 1, 2, 3, 8, 12, 16, 20, and 24. Patients were followed for acute, subacute, and chronic toxicity. Four patients (mean age 81.7 years) have been treated (NCT03743298). Three were treated with pembrolizumab. An 89-year-old female with recurrent stage 3 stopped treatment after five vaccine doses due to recurrent dermatologic toxicity that started during pembrolizumab and persisted during concurrent therapy. She remains recurrence-free 26 months after vaccine initiation. Two stage-4 patients received all 8 DC-ATA doses without toxicity. A 73-year-old female with stage 4b remains in complete remission 33 months after vaccine initiation. An 81-year-old male with stage 4b had a partial response, progressed after 6 months, but was still alive after 14 months. An 82-year-old male with stage 4c received pembrolizumab while DC-ATA was manufactured, then because of new brain metastases, received opdualag with DC-ATA. He had a partial response while receiving the eight vaccine doses but later progressed and died 10 months after vaccine initiation. In elderly patients with advanced melanoma, it appears that DC-ATA can be administered concurrently with anti-PD-1 without increased toxicity and with no decrease in efficacy. Additional testing of this combined immunotherapy is warranted. Citation Format: Chaitali S. Nangia, Katrina L. Lopez, Gabriel I. Nistor, Robert O. Dillman. Safety and efficacy of pembrolizumab plus personal dendritic cell vaccines in elderly patients with metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 651.