Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors

Abstract

Background Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. Methods Patients on ICIs who developed myocarditis ( n = 101) (cases) were compared to ICI-treated patients ( n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. Results The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls ( p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002). Conclusion The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV. Electronic supplementary material The online version of this article (10.1186/s40425-019-0535-y) contains supplementary material, which is available to authorized users.

On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19

“…In the latter subgroup, no negative influence on vaccination outcome was reported. 57 In this context, the study of Awadalla et al 65 should be pointed out. They actually demonstrated that the administration of a influenza vaccination was not correlated with an increased risk of subsequent myocarditis among patients on ICI.…”

“…Indeed, rates of vaccination were lower among patients who did develop ICI-induced myocarditis, and the vaccination was associated with a lower risk of other irAEs, in particular ICI-induced pneumonitis. 65 Unfortunately, there is little data available whether ICI would be beneficial in the management of severe influenza cases.…”

“…Indeed, rates of vaccination were lower among patients who did develop ICI-induced myocarditis, and the vaccination was associated with a lower risk of other irAEs, in particular ICI-induced pneumonitis. 65 Unfortunately, there is little data available whether ICI would be beneficial in the management of severe influenza cases. In this context, Yu et al 66 reported that influenza infection substantially increases the number of highly PD-1 positive innate lymphoid cells in the lungs of mice.…”

Cardiotoxicity of Contemporary Anticancer Immunotherapy

“…Similarly, while in a small study, influenza vaccination was associated with a higher rate of irAEs [ 20 ], in an international multicenter registry, the rate of influenza vaccination among ICI-related myocarditis cases was lower than the controls on ICIs who did not develop myocarditis, rejecting any such association of influenza vaccination with development of immune-mediated myocarditis. On the contrary, among those who developed ICI-associated myocarditis, the degree of myocardial injury and the risk of MACE were lower in patients who had received an influenza vaccine [ 21 ].…”

Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD‐1‐Antikörper beim metastasierten Melanom – ein Update

“…Seit der ersten berichteten Kardiomyopathie [93,94] zeigten sich verschiedene kardiale Nebenwirkungen wie Myokarditis mit hoher Mortalität [7,95], Perikarditis, Rhythmusstörungen und plötzlicher Herztod [96] [2,103].…”