Prospective investigation of immunotherapy-induced fatigue by rest and stress echocardiography.

Abstract

e24060 Background: Immune checkpoint inhibitors (ICI) effect durable responses in cancer patients (pts). Myocarditis is rare but fatigue is commonly reported, and whether ICI-induced fatigue is due to subclinical cardiac toxicity is unknown. We hypothesized that pts on ICI develop changes on rest and stress echocardiogram (echo) that correlate with fatigue. Methods: A prospective observational study was performed to monitor cardiac function in pts receiving ICI. Our cohort consisted of pts (n = 10) with stage III/IV melanoma, ECOG 0-1, deemed safe to exercise, without unstable cardiac symptoms. ICI-naïve pts received anti-PD1 alone or in combination with anti-CTLA-4, in adjuvant or metastatic setting. Rest transthoracic echo and dynamic staged exercise stress echo testing was conducted at baseline (prior to ICI) and at 3 and 6 months (mo) following ICI. Various echo parameters at rest and stress were compared. irAEs were detailed and surveys administered at baseline and post-follow up. Results: 10 pts (9 men, mean age 56 yrs) completed baseline cardiac testing of whom 7 completed follow up testing at 6 mo (6 anti-PD1 monotherapy, 1 metastatic combination therapy). Of these 7 pts, 5 (71%) reported increased fatigue per CTCAE at 3 or 6 mo follow up and all 7 had irAEs (3 rash, 1 colitis, 1 diarrhea, 1 hypophysitis, 1 arthralgia, 1 xerostomia). Among resting echo parameters, left ventricular outflow tract velocity time integral (LVOT VTI) was significantly reduced at 6 mo compared to baseline (22.6 ± 3.4 vs 20.0 ± 2.5, p = 0.0047), albeit still within normal range. No other resting echo parameters changed. Among exercise echo parameters, there was no difference in METs achieved, time of exercise, blood pressure or heart rate between time points. Of note, of 7 subjects who completed 6 mo testing, 2 (29%) were unable to achieve previous peak stage of exercise during testing. Conclusions: Though no echo parameter significantly correlating with fatigue was reported, nearly one-third of a small cohort of pts were unable to achieve peak exercise 6 mo after starting ICI. This combined with the statistical reduction in LVOT VTI suggests functional limitation and warrants further study. Post-follow up surveys are pending and may further inform issues important in ICI survivorship. [Table: see text]