Outcomes of immunotherapy in advanced melanoma in relation to age.

Abstract

187 Background: Older age is a risk feature in melanoma. Elderly are more likely to have immunosenescence, which could help melanoma cells escape immune surveillance. Hence, there is a belief that elderly people cannot mount a potent immune response to checkpoint inhibitors (CPI) to fully eliminate melanoma. The objective of the study was to investigate age-related differences in the time to progression (TTP), overall survival (OS), and immunotherapy related adverse events (irAEs) among patients with metastatic melanoma who received CPI. Methods: We retrospectively identified patients with stage IV melanoma who received at least 1 dose of ipilimumab, pembrolizumab, nivolumab, or combined ipilimumab and nivolumab. Demographics, pathologic, and clinical characteristics were obtained. Immune-related response criteria were utilized to define responses. Results: Sixty patients were included; 29 were less than 65 years old and 31 were 65 years or older. No significant differences, when adjusted for gender, type of melanoma and presence of brain metastasis, in TTP [HR 0.79; 95% CI (0.371.70); p = 0.46] and OS [Hazard ratio (HR) 0.75; 95% CI (0.31-1.82); P = 0.491] was observed between the < 65 and ≥65 year-old groups who received CPI for metastatic melanoma. Overall irAEs in two groups was comparable with 62% in the younger patients and 45% in the older patients (P = 0.19). Thirty responders had a median age of 66.9 (54.3-73.3 years old) and 30 non-responders had a median age of 62.7 (54-69.1 years old). Non-responders, regardless of age, were more likely to have BRAF mutated melanomas (53.3% vs. 27.6%; P = 0.04) and less likely to have irAEs (40% vs. 66.7%; P = 0.04) than responders. Conclusions: No difference in TTP, OS or irAEs was observed between the elderly and the young patients who received CPI for metastatic melanoma. In general, responders had higher irAEs and less BRAF mutated melanomas than non-responders.

Cutaneous malignant melanoma mortality in Spain from 1979 to 2018. Trends and new perspectives in the immunotherapy era

“…These treatments are generally well tolerated and have less adverse effects than classical chemotherapy. Hence, those groups of patients could benefit from them 28,29 . However, female >64 years old group showed a mortality rate plateau, with no downward curve in that period.…”

Molecular Landscape of Old Age Melanoma by Survival and Immunotherapy Response

“…Older patients respond to ICI (Joshi et al 2018;Kugel et al 2018;Perier-Muzet et al 2018;De Rosa et al 2018), and importantly, there are tumour immune-state response predictors (Balachandran et al 2017;Chowell et al 2018;McGranahan et al 2016;Rooney et al 2015;Topalian et al 2012) of poor outcome that are more prevalent in the young (Kugel et al 2018).…”

“…Untreated older melanoma patients have a significantly worse outcome, and the vast genomic differences that we show here following age-specific dissection of molecular data, supports the view that melanoma in elderly patients comprises a distinct group. Older patients respond to ICI (Joshi et al 2018; Kugel et al 2018; Perier-Muzet et al 2018; De Rosa et al 2018), and importantly, there are tumour immune-state response predictors (Balachandran et al 2017; Chowell et al 2018; McGranahan et al 2016; Rooney et al 2015; Topalian et al 2012) of poor outcome that are more prevalent in the young (Kugel et al 2018). High levels of accrued DNA damage, an established biomarker of ICI response in other cancer types(Samstein et al), is highly present in aged melanomas.…”

“…Older patients clearly stand to benefit from immunotherapy, and some reports suggest aged patients may present better response rates to immune checkpoint inhibitors (ICI) than younger patients (Joshi et al 2018; Kugel et al 2018; Perier-Muzet et al 2018; Ribas and Wolchok 2018; De Rosa et al 2018; Schadendorf et al 2018). ICI are currently being tested in the adjuvant, early stages of disease (Eggermont et al 2018b; Eggermont et al 2018a), but there are no validated rationales to stratify patients based on molecular evidence of risk of progression or response to therapy.…”

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

“…Although immunotherapy is a targeted therapy and therefore it is better tolerated compared to common chemotherapy, it has been associated with the emergence of a new panel of dysimmune toxicities called irAEs [ 9 , 118 – 120 ].…”