Abstract

Introduction: Myocarditis due to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event (irAE). Hypothesis: Limited data have suggested an association between baseline and on-treatment absolute lymphocyte count (ALC) and neutrophil lymphocyte ratio (NLR) and the development of other irAEs; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis. Methods: This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI irAEs. We leveraged clinical testing where patients underwent routine serial blood counts before and with each ICI cycle to compare the baseline and change in ALC and NLR between cases and controls. The association between the change in these parameters with clinical variables and major adverse cardiac events (MACE) was also tested. Results: In those who developed myocarditis, there was a decrease in ALC from baseline (1.6 K/μL, IQR 1.1-1.9) to admission (1.1 K/μL, IQR 0.7-1.3, p<0.001, Panel A). Similarly, among those who developed myocarditis, there was an increase in NLR from baseline (3.5, IQR 2.3-5.4) to admission (6.6, IQR 4.5-14.1, p<0.001, Panel B). There was no change in patients treated with an ICI who did not develop myocarditis. Among those who developed myocarditis, a greater decrease in ALC or increase in NLR was associated with a higher heart rate and a lower blood pressure at admission. In follow-up, there were 20 events; larger decreases in ALC or increases in NLR were associated with MACE (Panel C and D). Conclusions: A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR were associated with subsequent MACE.

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