University of Connecticut, Farmington, CT
Harsh V Parmar, Phil Kerr, Christina Elizabeth Stevenson, Sophie Masternak, Upendra P. Hegde
Background: Anti-PD-1 therapy has become an effective method of treating patients including elderly subjects diagnosed with un-resectable or metastatic melanoma. While effective, toxicity reports in elderly are conflicting. Some reports indicate no added autoimmunity with older melanoma patients, while we had previously reported our concerns of heightened autoimmune toxicity with anti-PD-1 treatment of melanoma in elderly subjects. This report includes updated results in 36 patients receiving anti-PD-1 treatment for melanoma with an increased proportion of older subjects from a single institute. Methods: Between 2014-2018, we performed retrospective review of charts of patients treated with anti-PD-1 agents for stage III and IV melanoma following IRB approval. Data for treatment outcomes and grade III and IV immune related adverse events were collected. Results: 36 patients were treated with either Pembrolizumab or Nivolumab that included stage IV melanoma (28 pts), un-resectable stage III (5 pts) and stage III melanoma in adjuvant setting (3 pts). 30 out of 36 patients were over 60 years of age (median age 77, range 62-90) and 6 patients were younger than 60 years (median age 48, range 24-56). 16 out of 30 patients over age of 60 years (53%) experienced grade III or IV toxicities following anti-PD-1 therapy compared to none (0%) in age below 60 years. Overall, 19 patients are alive either with disease or on treatment with stable, partial or complete responses. 17 patients have died, out of which 12 died of progressive disease, 2 elderly patients died suddenly and 3 elderly patients died of autoimmune toxicity (myasthenia gravis like syndrome, acute inflammatory demyelinating polyneuropathy, pneumonitis). Some unusual autoimmune toxicity seen in elderly subjects included diabetes mellitus, Behcet disease, acute inflammatory demyelinating polyneuropathy, retinitis, Bell's palsy and bullous pemphigoid). Conclusions: Our data continue to indicate that increased risk of severe autoimmune toxicity following anti-PD-1 treatment involved older patients over 60 years of age. This finding may highlight the increased susceptibility of autoimmunity with aging.
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