Impact of age on the toxicity of immune checkpoint inhibition

Abstract

Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (<65 years, 65-74 years and ≥75 years) using univariable and multivariable analyzes. Eligible patients (n=448) were divided into age cohorts: <65 years (n=185), 65-74 years (n=154) and ≥75 years (n=109). Fewer patients in the oldest cohort (7.3%) received an anti-CTLA4 antibody containing regimen compared with the younger cohorts (21.1% and 17.5%). There was no significant difference overall in all grade or ≥G3 toxicities between age cohorts. Significantly fewer patients in the older (65-74 years and ≥75 years) age cohorts discontinued treatment because of toxicity (10.1% and 7.4%) compared with in the <65 years cohort (20.5%; p=0.006). Using logistic regression, only treatment type (ipilimumab containing) was significantly associated with all grade toxicity. However, there was a significantly lower incidence of all-grade endocrine toxicity in the oldest cohort (11.0%) compared with the youngest cohort (22.7%, p=0.02; OR 0.43, 95% CI 0.21 to 0.87), while all-grade dermatological toxicity showed the reverse trend (28.4% vs 18.9%; OR 1.85, 95% CI 1.04 to 3.30). Results were corroborated in the sensitivity analysis using only data from patients who received PD-1 inhibitor monotherapy. This multicenter, real-world cohort demonstrates that immune checkpoint inhibitor therapy is safe and well tolerated regardless of age, with no appreciable increase in adverse events in older adult patients.

Keywords: immunotherapy; programmed cell death 1 receptor; self tolerance.

Figure 1

Treatment of ≥G3 toxicities. Patients were categorized into age groups (<65, 65–74 and ≥75 years). For each episode of toxicity, the most potent treatment modality only was recorded (non-steroid immunosuppressant>intravenous steroid>oral steroid>non-immunosuppressant only>no treatment). Non-steroid immunosuppressant treatment included biologics (eg, infliximab) and systemic immunosuppressants (eg, mycophenolate mofetil). Figures are shown as percentage of the total (for all age groups and each age group respectively). Treatment data were available for 302 patients.