Decreased Absolute Lymphocyte Count and Increased Neutrophil/Lymphocyte Ratio With Immune Checkpoint Inhibitor-Associated Myocarditis

Background Myocarditis attributable to immune checkpoint inhibitor (ICI) therapy is a potentially fatal immune-related adverse event. 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 immune-related adverse events; there are no data characterizing the role of ALC and NLR in ICI-associated myocarditis. Methods and Results This was a case control study of 55 patients with ICI myocarditis and 55 controls without any post-ICI immune-related adverse events. 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 was also tested. In cases, there was a statistically significant decrease in ALC with myocarditis from baseline (1.6 thousands per cubic milliliter (K/mu L); interquartile range, 1.1-1.9 K/mu L) to admission (1.1 K/mu L; interquartile range, 0.7-1.3 K/mu L; P<0.001). Similarly, there was an increase in NLR from baseline (3.5; interquartile range, 2.3-5.4) to admission (6.6; interquartile range, 4.5-14.1; P<0.001). There was no statistically significant change in controls. In follow-up, there were 20 events; larger decreases in ALC (44.6% versus 18.2%; P<0.001) or increases in NLR (156.5% versus 65.1%; P=0.019) were associated with major adverse cardiac events. Conclusions A reduction in ALC and an increase in NLR was seen with ICI myocarditis. A greater decrease in ALC or increase in NLR was associated with subsequent major adverse cardiac events.