Frailty and immunotherapy in melanoma: NI experience

Background: Pembrolizumab is an immune checkpoint inhibitor licensed for use in patients with melanoma. Melanoma is more common with increasing age, requiring oncologists to quantify suitability for immunotherapy. Currently, patient’s fitness for treatment is determined using the Eastern Cooperative Oncology Group (ECOG) performance status (PS) scale. Recently, the G8 frailty screening tool has been developed to enhance prognostic value in the geriatric oncology population.

Methods: Records of all patients treated with pembrolizumab for melanoma in the Northern Ireland Cancer Centre from January 2017 to January 2022 were reviewed. Independent variables were analysed for association with specific outcome measures, including maximum grade of toxicity, hospitalisation, and dose interruption, using Pearson’s chi-square test and Fisher’s exact test. Adverse events were graded as per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.

Results: Of 160 patients, 90 (56%) were male, median age was 71 years (range 23 – 88), and ECOG PS was 0/1/2 for 60(38%)/79(50%)/19(12%), respectively. Eighty-five patients (53%) received palliative intent treatment and 75 (47%) adjuvant intent. Toxicity was reported in 131 (82%) patients, 29 (18%) of these at ≥ Grade 3, 80 (50%) required a dose interruption in the first 18 weeks and 10 (6%) were hospitalised. Higher ECOG PS was significantly associated with hospitalisation (p=0.019) and dose interruption (p=0.028). Of the 8 components of the G8 score, we were retrospectively able to analyse three (Age, BMI, number of medications). Age and BMI were not associated with adverse outcomes; however, polypharmacy (≥ 3 medications) was more likely to result in a dose interruption (p=0.004).

Discussion: Pembrolizumab will be given to an increasingly frail cohort of patients. Oncologists require a prognostic tool to better reflect the heterogeneity of frailty. Improved screening for frailty in patients considering immunotherapy may help to highlight those more likely to suffer an adverse event.