Abstract
Abstract only e15158
Background: Anti-PD-1 agents produce durable responses in many cancers. However, the long-term impact of PD-1 blockade in terms of chronic toxicities, medical comorbidities, and HRQoL are not well-defined. Methods: We assessed 217 patients (pts) who received anti-PD-1 for melanoma, renal cell carcinoma or non-small cell lung carcinoma, with survival of > 2 years after treatment. Pt and tumor characteristics, immune related adverse events (irAEs), cardiometabolic parameters, body composition measurements (BCM), and HRQoL outcomes were tracked. Results: Median overall survival (OS) was not reached; 33 (15.2%) died during follow-up primarily from progressive cancer (n = 28). Acute irAEs developed during treatment in 65% of pts, 45.2% were grade 1/2, 35.5% required steroids, and most commonly presented with dermatitis (18.4%), thyroiditis (12.9%), or arthritis (9.7%). At last follow up, most pts were ECOG 0 (38%) or 1 (41%). There was no difference in blood pressure, glucose, or weight from baseline to 2 years after treatment initiation. BCM showed increased adiposity (140.1 vs. 144 cm
2
/m
2
, p = 0.05), skeletal muscle mass (47.05 vs. 47.72 cm
2
/m
2
, p = 0.03), and skeletal muscle gauge (1653.9 vs. 1671 AU, p = 0.04). The most common chronic irAEs at last follow-up included hypothyroidism (10.6%), arthritis (3.2%), adrenal insufficiency (3.2%), neuropathy (2.8%), pneumonitis (1.8%), and type 1 diabetes (0.8%). No pts died from chronic irAEs although one pt had fatal CNS radiation necrosis (with unknown contribution of ICI). Chronic irAEs were more common in pts treated with ipilimumab/nivolumab (49%) vs. those with monotherapy (26%). New comorbidities included type 2 diabetes (6.5%) and hypertension (6.0%). HRQoL at 2 years compared favorably to cancer and general populations, although younger age (p < 0.01) and need for subsequent therapy (p = 0.03) were associated with worse HRQoL using Functional Assessment of Cancer-General questionnaire (FACT-G). Acute irAEs were associated with worse National Comprehensive Cancer Network distress scores (p = 0.019). Conclusions: Durable responses to anti-PD-1 therapy and favorable HRQoL outcomes are encouraging in this long-term survivor population. Chronic irAEs may be more common than previously thought although no clear chronic adverse cardiometabolic effects were observed.