Lars Bastholt1, Henrik Schmidt2, Jon Kroll Bjerregaard3, Jørn Herrstedt4, Inge Marie Svane5. 1. Department of Clinical Oncology, Odense University Hospital, Odense, Denmark; Academy of Geriatric Cancer Research (AgeCare), Odense University Hospital, Odense, Denmark. Electronic address: lars.bastholt@rsyd.dk. 2. Department of Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Clinical Oncology, Odense University Hospital, Odense, Denmark. 4. Department of Clinical Oncology, Odense University Hospital, Odense, Denmark; Department of Clinical Oncology, Zealand University Hospital, Roskilde, Denmark. 5. Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Abstract
BACKGROUND AND PATIENTS: Age-related immune dysfunction (ARID) describes age-associated changes in immunity that may affect the efficacy of immunotherapy with checkpoint inhibitors. We evaluated the efficacy of treatment with ipilimumab (530 patients) or pembrolizumab (562 patients) in a Danish national cohort of metastatic melanoma patients. RESULTS: We confirmed known prognostic biomarkers related to treatment with ipilimumab and found no impact of age on survival or progression-free survival. In patients treated with pembrolizumab, we also confirmed known prognostic biomarkers. Overall survival (OS) and progression-free survival was significantly higher in patients aged between 70 and 80 years compared with younger patients. In multivariate analysis with OS as end-point, age was shown to be an independent good prognostic biomarker in these patients. Survival in patients aged above 80 years was not better than in younger patients, probably because of increase in significant comorbidity. CONCLUSIONS: Our analyses have revealed a higher survival rate when using drugs targeting PD1 in metastatic melanoma patients between the age of 70 and 80 years. ARID does not seem to negatively impact the efficacy of treatment with checkpoint inhibitors in metastatic melanoma patients. Despite these encouraging data for elderly patients, clinicians still need to carefully consider the higher risk of more serious outcomes of the immune-related adverse events in the elderly patient population, before deciding to treat old patients with checkpoint inhibitors.
BACKGROUND AND PATIENTS: Age-related immune dysfunction (ARID) describes age-associated changes in immunity that may affect the efficacy of immunotherapy with checkpoint inhibitors. We evaluated the efficacy of treatment with ipilimumab (530 patients) or pembrolizumab (562 patients) in a Danish national cohort of metastatic melanomapatients. RESULTS: We confirmed known prognostic biomarkers related to treatment with ipilimumab and found no impact of age on survival or progression-free survival. In patients treated with pembrolizumab, we also confirmed known prognostic biomarkers. Overall survival (OS) and progression-free survival was significantly higher in patients aged between 70 and 80 years compared with younger patients. In multivariate analysis with OS as end-point, age was shown to be an independent good prognostic biomarker in these patients. Survival in patients aged above 80 years was not better than in younger patients, probably because of increase in significant comorbidity. CONCLUSIONS: Our analyses have revealed a higher survival rate when using drugs targeting PD1 in metastatic melanomapatients between the age of 70 and 80 years. ARID does not seem to negatively impact the efficacy of treatment with checkpoint inhibitors in metastatic melanomapatients. Despite these encouraging data for elderly patients, clinicians still need to carefully consider the higher risk of more serious outcomes of the immune-related adverse events in the elderly patient population, before deciding to treat old patients with checkpoint inhibitors.
Authors: Mohammed Safi; Mahmoud Al-Azab; Chenxing Jin; Dario Trapani; Salem Baldi; Salah Adlat; Aman Wang; Bashir Ahmad; Hamza Al-Madani; Xiu Shan; Jiwei Liu Journal: Front Immunol Date: 2021-11-16 Impact factor: 7.561