The impact of patient age on toxicity and efficacy of immunotherapy agents.

Abstract

e15116 Background: Little data exists for the use of immune checkpoint inhibitors (ICI) in patients ≥80y old. Ageing is associated with immunosenescence, which may impact the efficacy and toxicity of immune-based therapies. Here we provide efficacy and immune related adverse event (irAE) data for patients ≥80y old and younger patient cohorts treated in routine clinical practice at 3 UK Cancer Centres: Guy’s and St Thomas’ NHS Foundation Trust, Oxford University Hospitals NHS Foundation Trust and University Hospitals of Leicester NHS Trust. Methods: Melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC) patients treated with ICIs between March 2016 – August 2018 were identified, and divided into five age-defined cohorts: < 50y, 50-59y, 60-69y, 70-79y, ≥80y. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method with data censored on 5th February 2018. Frequency and severity of five common irAEs were determined: hepatitis, endocrinopathies, immune-related gastrointestinal, skin and rheumatological. Results: 386 patients aged 22 – 98y (median 67y) received single-agent nivolumab (21%), pembrolizumab (62%), ipilimumab (10%) or combination ipilimumab and nivolumab (7%). 12% of patients were aged < 50y, 18% were 50-59y, 29% were 60-69y, 28% were 70-79y and 13% were ≥80y. Response rates (partial + complete response) were similar across all age groups (53% < 50y, 29% 50-59y, 48% 60-69y, 43% 70-79y and 47% ≥80y). Median PFS was 10.6, 10.3, 10.0, 5.8 and 19.7 months and OS was not reached, not reached, 29.0, 18.3, and 20.9 months for patients < 50y, 50-59y, 60-69y, 70-79y and ≥80y, respectively. The rate of any grade irAEs was lowest in patients ≥80y (59%), and highest in patients < 50y (92%). Grade 3-5 irAEs were also less frequent in patients ≥80y (10%) than those < 50y and 60-69y (both 18%). Conclusions: Of 386 patients 13% were ≥80y with response rates comparable to younger patient cohorts and rates of irAEs lower than younger patient cohorts in this retrospective analysis of a heterogenous patient population. Our data suggests that ICIs are well-tolerated and efficacious in elderly patients and that age alone should not preclude ICI use.

Safety of Immune Checkpoint Inhibitors in Elderly Patients: An Observational Study

“…A similar result has been reported in a real-world experience where the rate of any-grade irAEs was lowest in patients ≥80 years (59%), and highest in patients <50 years (92%). [27]. A well-tolerated profile of toxicities in the older patient age-groups has been reported in other retrospective analyses [18,28,29] in the Italian expanded access programs of nivolumab in NSCLC and in RCC, in programs of ipilimumab in melanoma [8,13,30] and in the phase 3B/4 checkmate 153 study, assessing nivolumab in patients with advanced NSCLC with poor prognostic features of advanced age or diminished ECOG PS [31].…”