Authors: Nangia Chaitali S, Lopez Katrina L, Dillman Robert O.
Background: Monoclonal antibodies that target programmed-death molecule-1 (anti-PD-1) are an effective immunotherapy for advanced melanoma. A promising investigational approach is a patient-specific therapeutic vaccine consisting of autologous dendritic cells pulsed with autologous tumor antigens from autologous tumor cells that are self-renewing in tissue culture. There is a strong rationale for combining these two immunotherapy approaches.
Patient and Methods: A 72-year-old White female was diagnosed with stage IVb metastatic melanoma confirmed by biopsies of lung and soft-tissue nodules. A short-term cell line was established from a 1.6 cm lung nodule. Autologous dendritic cells were differentiated from autologous monocytes obtained via leukapheresis. Per protocol, treatment was initiated with intravenous pembrolizumab every three weeks while the personal vaccine was manufactured. During the next 24 weeks, she received eight subcutaneous vaccine injections and eight more pembrolizumab infusions. After completing concurrent therapy, she continued pembrolizumab for an additional 27 months before stopping because of post-injection pruritus.
Results: Treatment was well-tolerated, both during the nine weeks of single-agent pembrolizumab as well as during the six months of concurrent immunotherapy. Just before starting the combined therapy, radiologic tests confirmed an objective partial response. Subsequently, her measurable disease continued to improve with SUV intensity decreased on PET scans and tumor size decreased on CT scans. One year after completing the vaccine, PET/CT scans were interpreted as showing a complete remission which was still ongoing 30 months later, 3.5 years after the initial diagnosis.
Conclusions: This personalized combination immunotherapy treatment is encouraging based on the lack of toxicity, confirmation of anti-tumor efficacy, and observed long-term disease control. Additional investigation of this combination is warranted.
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