Prognostic value of high-sensitivity Troponin I vs T in metastatic melanoma patients with immune checkpoint inhibitor-related low-risk myocarditis

Introduction

Immune checkpoint inhibitors (ICI) improve survival in metastatic melanoma patients but are limited by immune-related adverse (irAE ) events, among which myocarditis is a rare, but potentially high-risk complication.

Purpose

To evaluate the prognostic value of high-sensitivity troponin T and I (hsTnT, hsTnI) in ICI-related-myocarditis.

Methods

This retrospective study included 50 metastatic melanoma patients treated with ICI every 3 weeks. HsTnT and hsTnI were measured at baseline (T0) and at T1 (1–65 days), T2 (66–170 days), and T3 (171–335 days) after ICI initiation. Cardiac and oncologic data, ECG, and imaging were collected. Twenty-five patients with cardiac irAEs were matched 1:1 with age-, sex-, and ICI-regimen–matched controls. The irAE group was classified as clinical myocarditis (n=14; troponin elevation plus symptoms, ECG, or functional abnormalities) or subclinical myocarditis (n=11; troponin elevation only) according to ESC guidelines. Major adverse cardiovascular events (MACE: cardiovascular hospitalization) were recorded over a median 20-month follow-up (IQR 9–44). ROC curves and Youden index identified optimal hsTn cut-offs. Cox regression adjusted for age, sex, cardiovascular therapy, and chemotherapy.

Results

All irAE patients remained haemodynamically stable. Compared with controls (age 70 years [54–75], 48% female), patients with irAEs (age 64 years [49–73], 48% female) were more likely to receive dual ICI therapy (68% vs 32%, p=0.011) and ipilimumab (60% vs 32%, p=0.047). Baseline hsTn did not differ, but post-ICI levels were higher (hsTnTmax 95 [43–490] vs 11 [7–17] ng/L; hsTnImax 68 [26–199] vs 6.9 [3.4–10.3] ng/L; both p<0.001). Both hsTnTmax and hsTnImax showed good prognostic performance for MACE (hsTnTmax: AUC 0.869, 95%CI 0.77-0.97, p<0.001, specificity 68% and sensitivity 92% at a cut-off of 28ng/l; hsTnImax: AUC 0.833, 95%CI 0.70-0.97, p=0.001, specificity 67% and sensitivity 82% at a cut-off 54 ng/l). In multivariable Cox regression, hsTnI >54 ng/L was superior compared with hsTnT >28 ng/L as an independent predictor of MACE after adjustment for confounders (hsTnI>54 ng/L: HR 10–17.2, 95% CI 2.6–90.2, all p<0.001; hsTnT>28 ng/L: HR 14.7–17.4, 95% CI 1.9–134.7, p=0.006–0.011).

Patients with clinical myocarditis exhibited greater increases in both hsTnT and hsTnI from baseline compared with those with subclinical irAEs (ΔhsTnT: 176 ng/L [63–963] vs 52 ng/L [23–60], p=0.008; ΔhsTnI: 151.6 ng/L [59–327] vs 32.3 ng/L [10–69], p=0.026) and cardiovascular hospitalization was more frequent (79% vs 9%, p<0.001). Cancer outcomes (melanoma progression and death) did not differ.

Conclusions

In a cohort of metastatic melanoma patients with low-risk cardiac irAEs during ICI therapy, hsTnI showed superior prognostic performance compared with hsTnT as an independent predictor of cardiovascular hospitalization.Kaplan-Meier for MACE based on hsTnI